MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Advances in Pharmacology' source. Sat, 19 Nov 2011 02:24:09 +0100 http://www.medworm.com/index.php?rid=5234786&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907904%26dopt%3DAbstract Authors: PMID: 21907904 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=5234786 Tue, 20 Sep 2011 12:48:11 +0100 5234786 http://www.medworm.com/index.php?rid=5234785&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907905%26dopt%3DAbstract Authors: Congreve M, Langmead C, Marshall FH Abstract Structure-based drug discovery is routinely applied to soluble targets such as proteases and kinases. It is only recently that multiple high-resolution X-ray structures of G protein-coupled receptors (GPCRs) have become available. Here we review the technology developments that have led to the recent plethora of GPCR structures. These include developments in protein expression and purification as well as techniques to stabilize receptors and crystallize them. We discuss the findings derived from the new structures with regard to understanding GPCR function and pharmacology. Finally, we examine the utility of structure-based drug discovery approaches including homology modeling, virtual screening, and fragment screening for GPCRs... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=5234785 Tue, 20 Sep 2011 12:48:11 +0100 5234785 http://www.medworm.com/index.php?rid=5234784&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907906%26dopt%3DAbstract Authors: Sheffler DJ, Gregory KJ, Rook JM, Conn PJ Abstract The development of receptor subtype-selective ligands by targeting allosteric sites of G protein-coupled receptors (GPCRs) has proven highly successful in recent years. One GPCR family that has greatly benefited from this approach is the metabotropic glutamate receptors (mGlus). These family C GPCRs participate in the neuromodulatory actions of glutamate throughout the CNS, where they play a number of key roles in regulating synaptic transmission and neuronal excitability. A large number of mGlu subtype-selective allosteric modulators have been identified, the majority of which are thought to bind within the transmembrane regions of the receptor. These modulators can either enhance or inhibit mGlu functional responses and,... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=5234784 Tue, 20 Sep 2011 12:48:11 +0100 5234784 http://www.medworm.com/index.php?rid=5234783&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907907%26dopt%3DAbstract Authors: Gesty-Palmer D, Luttrell LM Abstract Early models of G protein-coupled receptor (GPCR) activation envisioned the receptor in equilibrium between unique "off" and "on" states, wherein ligand binding affected signaling by increasing or decreasing the fraction of receptors in the active conformation. It is now apparent that GPCRs spontaneously sample multiple conformations, any number of which may couple to one or more downstream effectors. Such "multistate" models imply that the receptor-ligand complex, not the receptor alone, defines which active receptor conformations predominate. "Functional selectivity" refers to the ability of a ligand to activate only a subset of its receptor's signaling repertoire. There are now numerous examples of ligands that "bias" receptor coupli... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=5234783 Tue, 20 Sep 2011 12:48:11 +0100 5234783 http://www.medworm.com/index.php?rid=5234782&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907908%26dopt%3DAbstract Authors: Conn PM, Ulloa-Aguirre A Abstract Structural alterations provoked by mutations or genetic variations in the gene sequence of G protein-coupled receptors (GPCRs) may lead to abnormal function of the receptor molecule. Frequently, this leads to disease. While some mutations lead to changes in domains involved in agonist binding, receptor activation, or coupling to effectors, others may cause misfolding and lead to retention/degradation of the protein molecule by the quality control system of the cell. Several strategies, including genetic, chemical, and pharmacological approaches, have been shown to rescue function of trafficking-defective misfolded GPCRs. Among these, pharmacological strategies offer the most promising therapeutic tool to promote proper trafficking of misfo... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=5234782 Tue, 20 Sep 2011 12:48:11 +0100 5234782 http://www.medworm.com/index.php?rid=5234781&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907909%26dopt%3DAbstract Authors: Huang Y, Cavanaugh A, Breitwieser GE Abstract Gain- or loss-of-function mutations and polymorphisms of the calcium-sensing receptor (CaSR) cause Ca(2+) handling diseases. Altered expression and/or signaling of wild-type CaSR can also contribute to pathology. Recent studies have demonstrated that a significant proportion of mutations cause altered targeting and/or trafficking of CaSR to the plasma membrane. Pharmacological approaches to rescue of CaSR function include treatment with allosteric modulators, which potentiate the effects of the orthosteric agonist Ca(2+). Dissection of the mechanism(s) contributing to allosteric agonist-mediated rescue of loss-of-function CaSR mutants has demonstrated pharmacologic chaperone actions coincident with CaSR biosynthesis. The distin... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=5234781 Tue, 20 Sep 2011 12:48:11 +0100 5234781 http://www.medworm.com/index.php?rid=5234780&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907910%26dopt%3DAbstract Authors: Hudson BD, Smith N, Milligan G Abstract The G protein-coupled receptors (GPCRs) are extremely successful drug targets, with recent estimates suggesting that approximately 30% of all currently available therapeutics act at these receptors. Despite this success, only a small number of the over 400 known nonodorant GPCRs are currently targeted, suggesting there is still untapped therapeutic potential. However, as most GPCRs were identified based on their sequence homology to other members of the superfamily, many still remain "orphan" receptors without known ligands. Indeed, even once a GPCR has been deorphanized, the receptor typically is still poorly characterized in terms of its pharmacology and biological functions, presenting a unique set of experimental challenges in or... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=5234780 Tue, 20 Sep 2011 12:48:11 +0100 5234780 http://www.medworm.com/index.php?rid=5234779&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907911%26dopt%3DAbstract Authors: Blad CC, Ahmed K, Ijzerman AP, Offermanns S Abstract The hydroxy-carboxylic acid (HCA) receptors HCA(1), HCA(2), and HCA(3) were previously known as GPR81, GPR109A, and GPR109B, respectively, or as the nicotinic acid receptor family. They form a cluster of G protein-coupled receptors with high sequence homology. Recently, intermediates of energy metabolism, all HCAs, have been reported as endogenous ligands for each of these receptors. The HCA receptors are predominantly expressed on adipocytes and mediate the inhibition of lipolysis by coupling to G(i)-type proteins. HCA(1) is activated by lactate, HCA(2) by the ketone body 3-hydroxy-butyrate, and HCA(3) by hydroxylated β-oxidation intermediates, especially 3-hydroxy-octanoic acid. Both HCA(2) and HCA(3) are part of a ne... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=5234779 Tue, 20 Sep 2011 12:48:11 +0100 5234779 http://www.medworm.com/index.php?rid=5234778&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907912%26dopt%3DAbstract Authors: Balenga NA, Henstridge CM, Kargl J, Waldhoer M Abstract According to The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), ∼70 million European adults have consumed cannabis on at least one occasion. Cannabis consumption leads to a variety of psychoactive effects due to the presence of the constituent Δ(9)-tetrahydrocannabinol (Δ(9)-THC). Δ(9)-THC interacts with the endocannabinoid system (ECS), which consists of the seven transmembrane spanning (7TM)/G protein-coupled receptors (GPCRs) CB(1) and CB(2), their respective ligands (endocannabinoids), and enzymes involved in their biosynthesis and degradation. This system plays a critical role in many physiological processes such as learning and memory, appetite control, pain sensation, motor coordination,... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=5234778 Tue, 20 Sep 2011 12:48:11 +0100 5234778 http://www.medworm.com/index.php?rid=5234777&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907913%26dopt%3DAbstract Authors: Romero G, von Zastrow M, Friedman PA Abstract PDZ proteins, named for the common structural domain shared by the postsynaptic density protein (PSD95), Drosophila disc large tumor suppressor (DlgA), and zonula occludens-1 protein (ZO-1), constitute a family of 200-300 recognized members. These cytoplasmic adapter proteins are capable of assembling a variety of membrane-associated proteins and signaling molecules in short-lived functional units. Here, we review PDZ proteins that participate in the regulation of signaling, trafficking, and function of G protein-coupled receptors. Salient structural features of PDZ proteins that allow them to recognize targeted GPCRs are considered. Scaffolding proteins harboring PDZ domains may contain single or multiple PDZ modules and may a... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=5234777 Tue, 20 Sep 2011 12:48:11 +0100 5234777 http://www.medworm.com/index.php?rid=5234776&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907914%26dopt%3DAbstract Authors: Sjögren B Abstract Regulators of G protein signaling (RGS) proteins have emerged in the past two decades as novel drug targets in many areas of research. Their importance in regulating signaling via G protein-coupled receptors has become evident as numerous studies have been published on the structure and function of RGS proteins. A number of genetic models have also been developed, demonstrating the potential clinical importance of RGS proteins in various disease states, including central nervous system disorders, cardiovascular disease, diabetes, and several types of cancer. Apart from their classical mechanism of action as GTPase-activating proteins (GAPs), RGS proteins can also serve other noncanonical functions. This opens up a new approach to targeting RGS proteins ... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=5234776 Tue, 20 Sep 2011 12:48:11 +0100 5234776 http://www.medworm.com/index.php?rid=5234775&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21907915%26dopt%3DAbstract Authors: Maurice P, Guillaume JL, Benleulmi-Chaachoua A, Daulat AM, Kamal M, Jockers R Abstract G protein-coupled receptors (GPCRs) are, with approximately 800 members, among the most abundant membrane proteins in humans. They are responding to a plethora of ligands and are involved in the transmission of extracellular signals inside the cell. GPCRs are synthesized in the endoplasmatic reticulum and are then transported to the cell surface where they are typically activated. Receptor activation triggers several processes such as signaling and receptor endocytosis. Along their life cycle, GPCRs are accompanied by a range of specialized GPCR-interacting proteins (GIPs) to assist nascent receptors in proper folding, to target them to the appropriate subcellular compartments and to ful... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=5234775 Tue, 20 Sep 2011 12:48:11 +0100 5234775 http://www.medworm.com/index.php?rid=4876708&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21586353%26dopt%3DAbstract Authors: Jacobson KA, Linden J PMID: 21586353 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4876708 Sun, 29 May 2011 21:00:02 +0100 4876708 http://www.medworm.com/index.php?rid=4876707&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21586354%26dopt%3DAbstract Authors: Lane JR, Jaakola VP, Ijzerman AP Extracellular adenosine mediates most of its physiological effects via an interaction with four G protein-coupled receptors (GPCRs), the adenosine receptors (ARs). These ARs are important pharmacological targets in the treatment of a wide variety of diseases from central nervous system disorders to ischemic injury. As for other GPCRs, drug development for the ARs has been hampered by the lack of structural data for this class of membrane proteins. However, in the past 3 years, this situation has changed with the elucidation of structures for the turkey β(1)-adrenoceptor, the human β(2)-adrenoceptor, squid rhodopsin, the activated form of bovine (rhod)opsin, the human adenosine A(2A) receptor, and most recently the CXCR4 chemokine receptor. In... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4876707 Sun, 29 May 2011 21:00:02 +0100 4876707 http://www.medworm.com/index.php?rid=4876706&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21586355%26dopt%3DAbstract Authors: Gessi S, Merighi S, Varani K, Borea PA The adenosine receptors A(1), A(2A), A(2B), and A(3) are important and ubiquitous mediators of cellular signaling, which play vital roles in protecting tissues and organs from damage. In particular, adenosine triggers tissue protection and repair by different receptor-mediated mechanisms, including an increase of oxygen supply/demand ratio, preconditioning, anti-inflammatory effects, and stimulation of angiogenesis. Considerable advances have been recently achieved in the pharmacological and molecular characterization of adenosine receptors, which have been proposed as targets for drug design and discovery. At the present time, it can be speculated that adenosine A(1), A(2A), A(2B), and A(3) receptor-selective ligands may show utility in ... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4876706 Sun, 29 May 2011 21:00:02 +0100 4876706 http://www.medworm.com/index.php?rid=4876705&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21586356%26dopt%3DAbstract Authors: Fredholm BB, Johansson S, Wang YQ Adenosine levels are increased under conditions of energy deprivation, both because intracellular energy stores are reduced and because ATP is released. The adenosine thus formed can serve to influence energy homeostasis in a number of different ways, besides alterations in blood supply and cellular work (including contraction, maintenance of membrane potential, and biosynthesis), which will be covered in other chapters. Here, effects on energy homeostasis will be briefly reviewed. Adenosine acting at the A(1) receptor is a powerful and nonredundant inhibitor of lipolysis. It increases glucose uptake in fat and muscle, but its effects on insulin secretion may be even more important than the actions at insulin target tissues. Glucagon is also i... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4876705 Sun, 29 May 2011 21:00:02 +0100 4876705 http://www.medworm.com/index.php?rid=4876704&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21586357%26dopt%3DAbstract Authors: Linden J The immune system responds to cues in the microenvironment to make acute and chronic adaptations in response to inflammation and injury. Locally produced purine nucleotides and adenosine provide receptor-mediated signaling to all bone-marrow derived cells of the immune system to modulate their responses. This review summarizes recent advances in our understanding of the effects of adenosine signaling through G protein-coupled adenosine receptors on cells of the immune system. Adenosine A(2A) receptors (A(2A)Rs) have a generally suppressive effect on the activation of immune cells. Moreover, their transcription is strongly induced by signals that activate macrophages or dendritic cells through toll-like receptors, or T cells through T cell receptors. A(2A)R induction i... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4876704 Sun, 29 May 2011 21:00:02 +0100 4876704 http://www.medworm.com/index.php?rid=4876703&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21586358%26dopt%3DAbstract Authors: Feoktistov I, Biaggioni I Recent progress in our understanding of the unique role of A(2B) receptors in the regulation of inflammation, immunity, and tissue repair was considerably facilitated with the introduction of new pharmacological and genetic tools. However, it also led to seemingly conflicting conclusions on the role of A(2B) adenosine receptors in inflammation with some publications indicating proinflammatory effects and others suggesting the opposite. This chapter reviews the functions of A(2B) receptors in various cell types related to inflammation and integrated effects of A(2B) receptor modulation in several animal models of inflammation. It is argued that translation of current findings into novel therapies would require a better understanding of A(2B) receptor f... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4876703 Sun, 29 May 2011 21:00:02 +0100 4876703 http://www.medworm.com/index.php?rid=4876702&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21586359%26dopt%3DAbstract Authors: Koeppen M, Eckle T, Eltzschig HK That adenosine signaling can elicit adaptive tissue responses during conditions of limited oxygen availability (hypoxia) is a long-suspected notion that recently gained general acceptance from genetic and pharmacologic studies of the adenosine signaling pathway. As hypoxia and inflammation share an interdependent relationship, these studies have demonstrated that adenosine signaling events can be targeted to dampen hypoxia-induced inflammation. Here, we build on the hypothesis that particularly the A(2B) adenosine receptor (ADORA(2B)) plays a central role in tissue adaptation to hypoxia. In fact, the ADORA(2B) requires higher adenosine concentrations than any of the other adenosine receptors. However, during conditions of hypoxia or ischemia, t... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4876702 Sun, 29 May 2011 21:00:02 +0100 4876702 http://www.medworm.com/index.php?rid=4876701&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21586360%26dopt%3DAbstract Authors: Jacobson KA, Gao ZG, Göblyös A, Ijzerman AP Among the purine and pyrimidine receptors, the discovery of small molecular allosteric modulators has been most highly advanced for the A(1) and A(3) adenosine receptors (ARs). These AR modulators have allosteric effects that are structurally separated from the orthosteric effects in SAR studies. The benzoylthiophene derivatives tend to act as allosteric agonists as well as selective positive allosteric modulators (PAMs) of the A(1) AR. A 2-amino-3-aroylthiophene derivative T-62 has been under development as a PAM of the A(1) AR for the treatment of chronic pain. Several structurally distinct classes of allosteric modulators of the human A(3) AR have been reported: 3-(2-pyridinyl)isoquinolines, 2,4-disubstituted quinolines, 1H-imid... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4876701 Sun, 29 May 2011 21:00:02 +0100 4876701 http://www.medworm.com/index.php?rid=4876700&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21586361%26dopt%3DAbstract Authors: Lazarowski ER, Sesma JI, Seminario-Vidal L, Kreda SM Given the widespread importance of purinergic receptor-evoked signaling, understanding how ATP and other nucleotides are released from cells in a regulated manner is an essential physiological question. Nonlytic release of ATP, UTP, UDP-glucose, and other nucleotides occurs in all cell types and tissues via both constitutive mechanisms, that is, in the absence of external stimuli, and to a greater extent in response to biochemical or mechanical/physical stimuli. However, a molecular understanding of the processes regulating nucleotide release has only recently begun to emerge. It is generally accepted that nucleotide release occurs in two different scenarios, exocytotic release from the secretory pathway or via conductive/tr... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4876700 Sun, 29 May 2011 21:00:02 +0100 4876700 http://www.medworm.com/index.php?rid=4876699&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21586362%26dopt%3DAbstract Authors: Kukulski F, Lévesque SA, Sévigny J P2 receptors that are activated by extracellular nucleotides (e.g., ATP, ADP, UTP, UDP, Ap(n)A) and P1 receptors activated by adenosine control a diversity of biological processes. The activation of these receptors is tightly regulated by ectoenzymes that metabolize their ligands. This review presents these enzymes as well as their roles in the regulation of P2 and P1 receptor activation. We focus specifically on the role of ectoenzymes in processes of our interest, that is, inflammation, vascular tone, and neurotransmission. An update on the development of ectonucleotidase inhibitors is also presented. PMID: 21586362 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4876699 Sun, 29 May 2011 21:00:02 +0100 4876699 http://www.medworm.com/index.php?rid=4876698&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21586363%26dopt%3DAbstract Authors: Deaglio S, Robson SC Evolving studies in models of transplant rejection, inflammatory bowel disease, and cancer, among others, have implicated purinergic signaling in clinical manifestations of vascular injury and thrombophilia, inflammation, and immune disturbance. Within the vasculature, spatial and temporal expression of CD39 nucleoside triphosphate diphosphohydrolase (NTPDase) family members together with CD73 ecto-5'-nucleotidase control platelet activation, thrombus size, and stability. This is achieved by closely regulated phosphohydrolytic activities to scavenge extracellular nucleotides, maintain P2-receptor integrity, and coordinate adenosinergic signaling responses. The CD38/CD157 family of extracellular NADases degrades NAD(+) and generates Ca(2+)-active metabolite... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4876698 Sun, 29 May 2011 21:00:02 +0100 4876698 http://www.medworm.com/index.php?rid=4876697&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21586364%26dopt%3DAbstract Authors: Burnstock G, Kennedy C Seven P2X receptor subunits have been cloned which form functional homo- and heterotrimers. These are cation-selective channels, equally permeable to Na(+) and K(+) and with significant Ca(2+) permeability. The three-dimensional structure of the P2X receptor is described. The channel pore is formed by the α-helical transmembrane spanning region 2 of each subunit. When ATP binds to a P2X receptor, the pore opens within milliseconds, allowing the cations to flow. P2X receptors are expressed on both central and peripheral neurons, where they are involved in neuromuscular and synaptic neurotransmission and neuromodulation. They are also expressed in most types of nonneuronal cells and mediate a wide range of actions, such as contraction of smooth muscle, se... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4876697 Sun, 29 May 2011 21:00:02 +0100 4876697 http://www.medworm.com/index.php?rid=4876696&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21586365%26dopt%3DAbstract Authors: von Kügelgen I, Harden TK The P2Y receptors are a widely expressed group of eight nucleotide-activated G protein-coupled receptors (GPCRs). The P2Y(1)(ADP), P2Y(2)(ATP/UTP), P2Y(4)(UTP), P2Y(6)(UDP), and P2Y(11)(ATP) receptors activate G(q) and therefore robustly promote inositol lipid signaling responses. The P2Y(12)(ADP), P2Y(13)(ADP), and P2Y(14)(UDP/UDP-glucose) receptors activate G(i) leading to inhibition of adenylyl cyclase and to Gβγ-mediated activation of a range of effector proteins including phosphoinositide 3-kinase-γ, inward rectifying K(+) (GIRK) channels, phospholipase C-β2 and -β3, and G protein-receptor kinases 2 and 3. A broad range of physiological responses occur downstream of activation of these receptors ranging from Cl(-) secretion by epithelia to ... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4876696 Sun, 29 May 2011 21:00:02 +0100 4876696 http://www.medworm.com/index.php?rid=4876695&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21586366%26dopt%3DAbstract In conclusion, P2Y receptors are important for the health of humans for many diseases, and we can expect even more beneficial drugs targeting P2Y receptors in the future. PMID: 21586366 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4876695 Sun, 29 May 2011 21:00:02 +0100 4876695 http://www.medworm.com/index.php?rid=4876694&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21586367%26dopt%3DAbstract Authors: Köles L, Leichsenring A, Rubini P, Illes P Purine and pyrimidine nucleotides are extracellular signaling molecules in the central nervous system (CNS) leaving the intracellular space of various CNS cell types via nonexocytotic mechanisms. In addition, ATP is a neuro-and gliotransmitter released by exocytosis from neurons and neuroglia. These nucleotides activate P2 receptors of the P2X (ligand-gated cationic channels) and P2Y (G protein-coupled receptors) types. In mammalians, seven P2X and eight P2Y receptor subunits occur; three P2X subtypes form homomeric or heteromeric P2X receptors. P2Y subtypes may also hetero-oligomerize with each other as well as with other G protein-coupled receptors. P2X receptors are able to physically associate with various types of ligand-gated i... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4876694 Sun, 29 May 2011 21:00:02 +0100 4876694 http://www.medworm.com/index.php?rid=4876693&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21586368%26dopt%3DAbstract Authors: Tozaki-Saitoh H, Tsuda M, Inoue K The purinergic receptor family contains some of the most abundant receptors in living organisms. A growing body of evidence indicates that extracellular nucleotides play important roles in the regulation of neuronal and glial functions in the nervous system through purinergic receptors. Nucleotides are released from or leaked through nonexcitable cells and neurons during normal physiological and pathophysiological conditions. Ionotropic P2X and metabotropic P2Y purinergic receptors are expressed in the central nervous system (CNS), participate in the synaptic processes, and mediate intercellular communications between neuron and gila and between glia and other glia. Glial cells in the CNS are classified into astrocytes, oligodendrocytes, and m... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4876693 Sun, 29 May 2011 21:00:02 +0100 4876693 http://www.medworm.com/index.php?rid=4187911&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21081212%26dopt%3DAbstract Authors: Vanhoutte M D Ph D PM PMID: 21081212 [PubMed - as supplied by publisher] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4187911 Sun, 21 Nov 2010 20:25:05 +0100 4187911 http://www.medworm.com/index.php?rid=4187910&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21081213%26dopt%3DAbstract In this report, we discuss the physiological and pathophysiological role of endothelium-derived ET-1, the pharmacology of its two receptors, focusing on the regulation of the vascular tone and as much as possible in humans. The coronary bed will be used as a running example, but references to the pulmonary, cerebral, and renal circulation will also be made. Many of the cardiovascular complications associated with aging and cardiovascular risk factors are initially attributable, at least in part, to endothelial dysfunction, particularly dysregulation of the vascular function associated with an imbalance in the close interdependence of NO and ET-1, in which the implication of the ET(B) receptor may be central. PMID: 21081213 [PubMed - as supplied by publisher] (Source: Advances in Pharma... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4187910 Sun, 21 Nov 2010 20:25:05 +0100 4187910 http://www.medworm.com/index.php?rid=4187909&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21081214%26dopt%3DAbstract Authors: Pfister SL, Gauthier KM, Campbell WB Epoxyeicosatrienoic acids (EETs) are cytochrome P450 metabolites of arachidonic acid that are produced by the vascular endothelium in responses to various stimuli such as the agonists acetylcholine (ACH) or bradykinin or by shear stress which activates phospholipase A(2) to release arachidonic acid. EETs are important regulators of vascular tone and homeostasis. In the modulation of vascular tone, EETs function as endothelium-derived hyperpolarizing factors (EDHFs). In models of vascular inflammation, EETs attenuate inflammatory signaling pathways in both the endothelium and vascular smooth muscle. Likewise, EETs regulate blood vessel formation or angiogenesis by mechanisms that are still not completely understood. Soluble epoxide hydrolase... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4187909 Sun, 21 Nov 2010 20:25:05 +0100 4187909 http://www.medworm.com/index.php?rid=4187908&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21081215%26dopt%3DAbstract Authors: Wong SL, Wong WT, Tian XY, Lau CW, Huang Y Endothelium regulates local vascular tone by means of releasing relaxing and contracting factors, of which the latter have been found to be elevated in vascular pathogenesis of hypertension, diabetes, hypercholesterolemia, and aging. Endothelium-derived contracting factors (EDCFs) are mainly metabolites of arachidonic acid generated by cyclooxygenase (COX), as vasodilatations in patients with hypertension, metabolic diseases, or advancing age are improved by acute treatment with COX inhibitor indomethacin. COX is presented in two isoforms, COX-1 and COX-2, with the former regarded as constitutive and the latter mainly expressed upon induction. Experiments with animal models of vascular dysfunctions, however, reveal that both isoforms ... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4187908 Sun, 21 Nov 2010 20:25:05 +0100 4187908 http://www.medworm.com/index.php?rid=4187907&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21081216%26dopt%3DAbstract Authors: Félétou M, Cohen RA, Vanhoutte PM, Verbeuren TJ Thromboxane A(2) and the activation of TP receptors that it causes play an important role in platelet aggregation and therefore in thrombosis. However, TP receptors are also involved in the pathologies of the vascular wall including impaired endothelium-dependent vasodilation, increased oxidant generation, and increased expression of adhesion molecules. The beneficial effects of TP antagonists on the vascular wall attenuate these features of vascular disease. They are not shared by aspirin. In fact, TP antagonists are active in patients treated with aspirin, indicating that their potential beneficial effects are mediated by mechanisms different from the antithrombotic actions of aspirin. Our studies have demonstrated the vascul... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4187907 Sun, 21 Nov 2010 20:25:05 +0100 4187907 http://www.medworm.com/index.php?rid=4187906&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21081217%26dopt%3DAbstract Authors: Harrison DG, Chen W, Dikalov S, Li L Tetrahydrobiopterin (BH(4)) is a critical cofactor for the nitric oxide synthases. In the absence of BH(4), these enzymes become uncoupled, fail to produce nitric oxide, and begin to produce superoxide and other reactive oxygen species (ROS). BH(4) levels are modulated by a complex biosynthetic pathway, salvage enzymes, and by oxidative degradation. The enzyme GTP cyclohydrolase-1 catalyzes the first step in the de novo synthesis of BH(4) and new evidence shows that this enzyme is regulated by phosphorylation, which reduces its interaction with its feedback regulatory protein (GFRP). In the setting of a variety of common diseases, such as atherosclerosis, hypertension, and diabetes, reactive oxygen species promote oxidation of BH(4) and inh... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4187906 Sun, 21 Nov 2010 20:25:05 +0100 4187906 http://www.medworm.com/index.php?rid=4187905&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21081218%26dopt%3DAbstract Authors: Schini-Kerth VB, Auger C, Etienne-Selloum N, Chataigneau T The Mediterranean diet has been associated with greater longevity and quality of life in epidemiological studies. Indeed, because of the abundance of fruits and vegetables and a moderate consumption of wine, the Mediterranean diet provides high amounts of polyphenols thought to be essential bioactive compounds that might provide health benefits in terms of cardiovascular diseases and mortality. Several polyphenol-rich sources, such as grape-derived products, cocoa, and tea, have been shown to decrease mean blood pressure in patients with hypertension. The improvement of the endothelial function is likely to be one of the mechanisms by which polyphenols may confer cardiovascular protection. Indeed, polyphenols are able ... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4187905 Sun, 21 Nov 2010 20:25:05 +0100 4187905 http://www.medworm.com/index.php?rid=4187904&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21081219%26dopt%3DAbstract Authors: Daiber A, Münzel T, Gori T The hemodynamic and antiischemic effects of nitroglycerin (GTN) are lost upon chronic administration due to the rapid development of nitrate tolerance. The mechanism of this phenomenon has puzzled several generations of scientists, but recent findings have led to novel hypotheses. The formation of reactive oxygen and nitrogen species in the mitochondria and the subsequent inhibition of the nitrate-bioactivating enzyme mitochondrial aldehyde dehydrogenase (ALDH-2) appear to play a central role, at least for GTN, that is, bioactivated by ALDH-2. Importantly, these findings provide the opportunity to reconcile the two "traditional" hypotheses of nitrate tolerance, that is, the one postulating a decreased bioactivation and the concurrent one suggesting ... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4187904 Sun, 21 Nov 2010 20:25:05 +0100 4187904 http://www.medworm.com/index.php?rid=4187903&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21081220%26dopt%3DAbstract Authors: Xu A, Wang Y, Lam KS, Vanhoutte PM Adipose tissue is a critical regulator of vascular function, which until recently had been virtually ignored. Almost all blood vessels are surrounded by perivascular adipose tissue, which is actively involved in the maintenance of vascular homeostasis by producing "vasocrine" signals such as adipokines. Adiponectin and adipocyte fatty acid binding protein (A-FABP), both of which are major adipokines predominantly produced in adipose tissue, have recently been shown to be pivotal modulators of vascular function. Adiponectin has multiple beneficial effects on cardiovascular health. It prevents obesity-induced endothelial dysfunction by inducing nitric oxide production, suppressing endothelial cell activation, inhibiting reactive oxygen species ... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4187903 Sun, 21 Nov 2010 20:25:05 +0100 4187903 http://www.medworm.com/index.php?rid=4187902&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21081221%26dopt%3DAbstract Authors: Santhanam AV, d'Uscio LV, Katusic ZS Erythropoietin (EPO) is a therapeutic product of recombinant DNA technology and it has been in clinical use as stimulator of erythropoiesis over the last two decades. Identification of EPO and its receptor (EPOR) in the cardiovascular system expanded understanding of physiological and pathophysiological role of EPO. In experimental models of cardiovascular and cerebrovascular disorders, EPO exerts protection either by preventing apoptosis of cardiac myocytes, smooth muscle cells, and endothelial cells, or by increasing endothelial production of nitric oxide. In addition, EPO stimulates mobilization of progenitor cells from bone marrow thereby accelerating repair of injured endothelium and neovascularization. A novel signal transduction path... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4187902 Sun, 21 Nov 2010 20:25:05 +0100 4187902 http://www.medworm.com/index.php?rid=4140607&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21038478%26dopt%3DAbstract Authors: PMID: 21038478 [PubMed - indexed for MEDLINE] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4140607 Sun, 07 Nov 2010 20:50:03 +0100 4140607 http://www.medworm.com/index.php?rid=4066700&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20933196%26dopt%3DAbstract Authors: Vanhoutte P PMID: 20933196 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4066700 Fri, 15 Oct 2010 09:55:03 +0100 4066700 http://www.medworm.com/index.php?rid=4066699&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20933197%26dopt%3DAbstract Authors: Kushnir A, Marks AR According to the American Heart Association it is estimated that the United States will spend close to $39 billion in 2010 to treat over five million Americans suffering from heart failure. Patients with heart failure suffer from dyspnea and decreased exercised tolerance and are at increased risk for fatal ventricular arrhythmias. Food and Drug Administration -approved pharmacologic therapies for heart failure include diuretics, inhibitors of the renin-angiotensin system, and β-adrenergic receptor antagonists. Over the past 20 years advances in the field of ryanodine receptor (RyR2)/calcium release channel research have greatly advanced our understanding of cardiac physiology and the pathogenesis of heart failure and arrhythmias. Here we review the key obs... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4066699 Fri, 15 Oct 2010 09:55:03 +0100 4066699 http://www.medworm.com/index.php?rid=4066698&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20933198%26dopt%3DAbstract Authors: Xu Y, Li X, Liu X, Zhou M Neuregulin-1 (NRG-1), a cardioactive growth factor released from endothelial cells, is indispensable for cardiac development, structural maintenance, and functional integrity of the heart. In recent years, a growing number of studies have focused on NRG-1 and members of the ErbB family that serve as receptors for NRG-1 in order to better understand the role of this signaling pathway in physiology and pathophysiology of the heart. An essential role for NRG-1 and ErbB in heart development and functionality has been suggested by studies in conditional NRG-1/ErbB-deficient mice and by the cardiac-related side effects of anti-ErbB2 antibody therapies used for treatment of breast cancer. In vitro and in vivo studies using recombinant human neuregulin-1 (rhN... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4066698 Fri, 15 Oct 2010 09:55:03 +0100 4066698 http://www.medworm.com/index.php?rid=4066697&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20933199%26dopt%3DAbstract Authors: Thollon C, Vilaine JP Heart rate (HR) is determined by the pacemaker activity of cells from the sinoatrial node (SAN), located in the right atria. Spontaneous electrical activity of SAN cells results from a diastolic depolarization (DD). Despite controversy in the exact contribution of funny current (I(f)) in pacemaking, it is a major contributor of DD. I(f) is an inward Na(+)/K(+) current, activated upon hyperpolarization and directly modulated by cyclic adenosine monophosphate. The f-proteins are hyperpolarization-activated cyclic nucleotide-gated channels, HCN4 being the main isoform of SAN. Ivabradine (IVA) decreases DD and inhibits I(f) in a use-dependent manner. Under normal conditions IVA selectively reduces HR and limits exercise-induced tachycardia, in animals and you... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4066697 Fri, 15 Oct 2010 09:55:03 +0100 4066697 http://www.medworm.com/index.php?rid=4066696&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20933200%26dopt%3DAbstract Authors: Li GR, Dong MQ Cardiac K(+) channels are cardiomyocyte membrane proteins that regulate K(+) ion flow across the cell membrane on the electrochemical gradient and determine the resting membrane potential and the cardiac action potential morphology and duration. Several K(+) channels have been well studied in the human heart. They include the transient outward K(+) current I(to1), the ultra-rapidly activating delayed rectifier current I(Kur), the rapidly and slowly activating delayed rectifier currents I(Kr) and I(Ks), the inward rectifier K(+) current I(K1), and ligand-gated K(+) channels, including adenosine-5'-triphosphate (ATP)-sensitive K(+) current (I(KATP)) and acetylcholine-activated current (I(KACh)). Regional differences of K(+) channel expression contribute to the var... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4066696 Fri, 15 Oct 2010 09:55:03 +0100 4066696 http://www.medworm.com/index.php?rid=4066695&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20933201%26dopt%3DAbstract Authors: Dessy C, Balligand JL Catecholamines released by the orthosympathetic system play a major role in the short- and long-term regulation of cardiovascular function. Beta1- and beta2-adrenoreceptors (ARs) have classically been considered as mediating most of their effects on cardiac contraction. After their initial cloning and pharmacologic characterization in the late 1980s, beta3-ARs have been mostly thought of as receptors mediating metabolic effects (e.g., lipolysis) in adipocytes. However, definitive evidence for their expression and functional coupling in cardiovascular tissues (including in humans) has recently initiated a re-examination of their implication in the pathophysiology of cardiovascular diseases. Distinctive pharmacodynamic properties of beta3-AR, e.g., their up... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4066695 Fri, 15 Oct 2010 09:55:03 +0100 4066695 http://www.medworm.com/index.php?rid=4066694&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20933202%26dopt%3DAbstract Authors: Adachi T Endothelial dysfunction associated with decreased nitric oxide (NO) bioactivity is a major feature of vascular diseases such as atherosclerosis or diabetes. Sodium nitroprusside (SNP)-induced relaxation is entirely dependent on cyclic guanosine monophosphate (cGMP) and preserved in atherosclerosis, suggesting that smooth muscle response to NO donor is intact. However, NO gas activates both cGMP-dependent and -independent signal pathways in vascular smooth muscle cells, and oxidative stress associated with vascular diseases selectively impairs cGMP-independent relaxation to NO. Sarco/endoplasmic reticulum Ca(2+) ATPase (SERCA), which regulates intracellular Ca(2+) levels by pumping Ca(2+) into store, is a major cGMP-independent target for NO. Physiological levels of re... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4066694 Fri, 15 Oct 2010 09:55:03 +0100 4066694 http://www.medworm.com/index.php?rid=4066693&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20933203%26dopt%3DAbstract Authors: Ferrario CM, Ahmad S, Joyner J, Varagic J The contribution of the renin angiotensin system to physiology and pathology is undergoing a rapid reconsideration of its mechanisms from emerging new concepts implicating angiotensin-converting enzyme 2 and angiotensin-(1-7) as new elements negatively influencing the vasoconstrictor, trophic, and pro-inflammatory actions of angiotensin II. This component of the system acts to oppose the vasoconstrictor and proliferative effects on angiotensin II through signaling mechanisms mediated by the mas receptor. In addition, a reduced expression of the vasodepressor axis composed by angiotensin-converting enzyme 2 and angiotensin-(1-7) may contribute to the expression of essential hypertension, the remodeling of heart and renal function associ... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4066693 Fri, 15 Oct 2010 09:55:03 +0100 4066693 http://www.medworm.com/index.php?rid=4066692&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20933204%26dopt%3DAbstract Authors: Randriamboavonjy V, Fleming I Diabetes mellitus is a major risk factor for vascular diseases and is associated with accelerated atherosclerosis and a high rate of arterial thrombotic complications. A number of studies support the concept that platelets contribute to the pathogenesis and progression of the vascular complications of diabetes. µ-Calpain, a non-lysosomal, Ca(2+)-dependent cysteine protease, is expressed in platelets and is involved in physiological platelet activation. However, the inappropriate activation of calpain alters platelet function, partially degrades a spectrum of proteins and results in hyperaggregability. Changes in the activity of calpain in different cells involved in diabetes-related pathways, or the polymorphism of calpain genes have been associa... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4066692 Fri, 15 Oct 2010 09:55:03 +0100 4066692 http://www.medworm.com/index.php?rid=4066691&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20933205%26dopt%3DAbstract Authors: Holy EW, Tanner FC Tissue factor (TF) is the major trigger of the coagulation cascade and thereby crucially involved in the maintenance of vascular hemostasis. By binding factor VIIa, the resulting TF:VIIa complex activates the coagulation factors IX and X ultimately leading to fibrin and clot formation. In the vessel wall, TF expression and activity is detectable in vascular smooth muscle cells and fibroblasts and, at a much lower level, in endothelial cells and can be induced by various stimuli including cytokines. In addition, TF is found in the bloodstream in circulating cells such as monocytes, in TF containing microparticles, and as a soluble splicing isoform. Besides its well-known extracellular role as a trigger of coagulation, TF also functions as a transmembrane rece... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=4066691 Fri, 15 Oct 2010 09:55:03 +0100 4066691 http://www.medworm.com/index.php?rid=3797941&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20655475%26dopt%3DAbstract Authors: Enna SJ, Blackburn TP PMID: 20655475 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=3797941 Thu, 29 Jul 2010 07:45:04 +0100 3797941 http://www.medworm.com/index.php?rid=3797940&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20655476%26dopt%3DAbstract Authors: Bowery NG This chapter forms an introduction to the subsequent chapters in this volume which highlight the significance and potential therapeutic application of GABA(B) receptors. It is now 30 years since the GABA(B) site was first described in mammalian tissue. Since then much has emerged about its physiological role in the mammalian nervous system and its relationship to other neurotransmitter receptors. It appears to function at pre- and postsynaptic locations as both an auto- and a hetero-receptor where its activation modulates the membrane conductance of Ca(2+) and K(+). The receptor is G-protein coupled and was the first to be shown to exist, possibly in multiple forms, as a heterodimer. The primary agonist for the receptor is baclofen and this continues to be used thera... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=3797940 Thu, 29 Jul 2010 07:45:04 +0100 3797940 http://www.medworm.com/index.php?rid=3797939&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20655477%26dopt%3DAbstract Authors: Froestl W This chapter presents new clinical applications of the prototypic GABA(B) receptor agonist baclofen for the treatment of addiction by drugs of abuse, such as alcohol, cocaine, nicotine, morphine, and heroin, a novel baclofen prodrug Arbaclofen placarbil, the GABA(B) receptor agonist AZD3355 (Lesogabaran) currently in Phase 2 clinical trials for the treatment of gastroesophageal reflux disease, and four positive allosteric modulators of GABA(B) receptors (CGP7930, GS39783, NVP-BHF177, and BHFF), which have less propensity for the development of tolerance due to receptor desensitization than classical GABA(B) receptor agonists. All four compounds showed anxiolytic affects. In the presence of positive allosteric modulators the "classical" GABA(B) receptor antagonists CG... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=3797939 Thu, 29 Jul 2010 07:45:04 +0100 3797939 http://www.medworm.com/index.php?rid=3797929&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20655478%26dopt%3DAbstract Authors: Marshall FH, Foord SM The identification of the molecular nature of the GABA(B) receptor and the demonstration of its heterodimeric structure has led to extensive studies investigating the mechanism of activation and signaling. Phylogenetic studies suggest that the formation of the heterodimer is a relatively recent event arising in conjunction with the evolution of the central nervous system. Heterodimerization has now been demonstrated for many other G-protein-coupled receptors (GPCRs) and plays a role in signaling and trafficking. This presents both challenges and opportunities for GPCR drug discovery. In the case of the GABA(B) receptor the best hope for the development of new drugs directed at this receptor is from allosteric modulators. This chapter summarizes our curren... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=3797929 Thu, 29 Jul 2010 07:45:04 +0100 3797929 http://www.medworm.com/index.php?rid=3797915&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20655479%26dopt%3DAbstract Authors: Benke D GABA(B) receptors belong to the family of G-protein-coupled receptors, which mediate slow inhibitory neurotransmission in the central nervous system. They are promising drug targets for a variety of neurological disorders and play important functions in regulating synaptic plasticity. Signaling strength is critically dependent on the availability of the receptors at the cell surface. Several distinct highly regulated trafficking mechanisms ensure the presence of adequate receptor numbers in the plasma membrane. The rate of exocytosis of newly synthesized receptors from the endoplasmic reticulum via the Golgi apparatus to the cell surface as well as the rates of their endocytosis and degradation determines the retention time of receptors at the cell surface. This chapte... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=3797915 Thu, 29 Jul 2010 07:45:04 +0100 3797915 http://www.medworm.com/index.php?rid=3797914&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20655480%26dopt%3DAbstract Authors: Terunuma M, Pangalos MN, Moss SJ GABA(B) receptors (GABA(B)R) are heterodimeric G protein-coupled receptors (GPCRs) that mediate slow and prolonged inhibitory signals in the central nervous system. The signaling of GPCRs is under stringent control and is subject to regulation by multiple posttranslational mechanisms. The beta-adrenergic receptor is a prototypic GPCR. Like most GPCRs, prolonged exposure of this receptor to agonist induces phosphorylation of multiple intracellular residues that is largely dependent upon the activity of G protein-coupled receptor kinases (GRKs). Phosphorylation terminates receptor-effector coupling and promotes both interaction with beta-arrestins and removal from the plasma membrane via clathrin-dependent endocytosis. Emerging evidence for GABA(... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=3797914 Thu, 29 Jul 2010 07:45:04 +0100 3797914 http://www.medworm.com/index.php?rid=3797913&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20655481%26dopt%3DAbstract Authors: Padgett CL, Slesinger PA GABA(B) receptors have been found to play a key role in regulating membrane excitability and synaptic transmission in the brain. The GABA(B) receptor is a G-protein coupled receptor (GPCR) that associates with a subset of G-proteins (pertussis toxin sensitive Gi/o family), that in turn regulate specific ion channels and trigger cAMP cascades. In this review, we describe the relationships between the GABA(B) receptor, its effectors and associated proteins that mediate GABA(B) receptor function within the brain. We discuss a unique feature of the GABA(B) receptor, the requirement for heterodimerization to produce functional receptors, as well as an increasing body of evidence that suggests GABA(B) receptors comprise a macromolecular signaling heterocompl... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=3797913 Thu, 29 Jul 2010 07:45:04 +0100 3797913 http://www.medworm.com/index.php?rid=3797909&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20655482%26dopt%3DAbstract Authors: Tabata T, Kano M In mammalian brains, gamma-amino butyric acid (GABA) is the most ubiquitous inhibitory neurotransmitter and neuromodulator. The G(i/o) protein-coupled GABA receptor termed B-type GABA receptor (GABA(B)R) has been recognized as one of the major mediators of the inhibitory effects of GABA. Several years ago, Hirono et al. and our group independently found that GABA(B)R mediates non-inhibitory effects in cerebellar Purkinje cells. In this cell type, GABA(B)R co-localizes with type-1 metabotropic glutamate receptor (mGluR1), a G(q/11) protein-coupled receptor around the postsynaptic membrane of the excitatory synapses. At that site, GABA(B)R is not exposed to the direct bombardment of GABA released from the terminals of inhibitory neurons. Instead, the receptor ma... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=3797909 Thu, 29 Jul 2010 07:45:04 +0100 3797909 http://www.medworm.com/index.php?rid=3797905&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20655483%26dopt%3DAbstract Authors: Gonzalez-Burgos G The GABA transporter 1 (GAT1), the main plasma membrane GABA transporter in brain tissue, mediates translocation of GABA from the extracellular to the intracellular space. Whereas GAT1-mediated uptake could generally terminate the synaptic effects of GABA, recent studies suggest a more complex physiological role. This chapter reviews evidence suggesting that in hippocampal and neocortical circuits, GAT1-mediated GABA transport regulates the electrophysiological effects of GABA(B) receptor (GABA(B)R) activation by synaptically-released GABA. Contrasting with synaptic GABA(A) receptors, GABA(B)Rs display high GABA binding affinity, slow G protein-coupled mediated signaling, and a predominantly extrasynaptic localization. Such GABA(B)R properties determine produ... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=3797905 Thu, 29 Jul 2010 07:45:04 +0100 3797905 http://www.medworm.com/index.php?rid=3797902&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20655484%26dopt%3DAbstract Authors: Kohl MM, Paulsen O Temporally-structured cortical activity in the form of synchronized network oscillations and persistent activity is fundamental for cognitive processes such as sensory processing, motor control, working memory, and consolidation of long-term memory. The roles of fast glutamatergic excitation via AMPA, kainate, and NMDA receptors, as well as fast GABAergic inhibition via GABA(A) receptors, in such network activity have been studied in great detail. In contrast, we have only recently begun to appreciate the roles of slow inhibition via GABA(B) receptors in the control of cortical network activity. Here, we provide a framework for understanding the contributions of GABA(B) receptors in helping mediate, modulate, and moderate different types of physiological and... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=3797902 Thu, 29 Jul 2010 07:45:04 +0100 3797902 http://www.medworm.com/index.php?rid=3797883&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20655485%26dopt%3DAbstract Authors: Pinard A, Seddik R, Bettler B GABA(B) receptors are the G-protein-coupled receptors (GPCRs) for gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the central nervous system. GABA(B) receptors are implicated in the etiology of a variety of psychiatric disorders and are considered attractive drug targets. With the cloning of GABA(B) receptor subunits 13 years ago, substantial progress was made in the understanding of the molecular structure, physiology, and pharmacology of these receptors. However, it remained puzzling that native studies demonstrated a heterogeneity of GABA(B) responses that contrasted with a very limited diversity of cloned GABA(B) receptor subunits. Until recently, the only firmly established molecular diversity consisted of two GABA(B1)... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=3797883 Thu, 29 Jul 2010 07:45:04 +0100 3797883 http://www.medworm.com/index.php?rid=3797858&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20655486%26dopt%3DAbstract Authors: Li DP, Pan HL GABA(B) receptors belong to family III G protein-coupled receptors (GPCRs) and are widely distributed in the peripheral and central nervous systems. The GABA(B) receptor is one of the most important therapeutic targets in the treatment for spasticity. GABA(B) agonists, such as baclofen, are used as muscle relaxants clinically and are effective for the treatment of anxiety, depression, epilepsy, and cognitive disorders (Caddick & Hosford, 1996; Dichter, 1997; Enna & Bowery, 1997). In addition, GABA(B) receptors regulate neurotransmitter release and neuronal excitability in the brain regions involved in the autonomic nervous system. Recent studies have led to a better understanding of the role of GABA(B) in the regulation of the autonomic nervous system, es... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=3797858 Thu, 29 Jul 2010 07:45:04 +0100 3797858 http://www.medworm.com/index.php?rid=3797851&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20655487%26dopt%3DAbstract Authors: Lehmann A, Jensen JM, Boeckxstaens GE Defined pharmacologically by its insensitivity to the GABA(A) antagonist bicuculline and sensitivity to the GABA analogue baclofen, the G protein-linked gamma-aminobutyric acid type B (GABA(B)) receptor couples to adenylyl cyclase, voltage-gated calcium channels, and inwardly-rectifying potassium channels. On the basis of a wealth of preclinical data in conjunction with early clinical observations that baclofen improves symptoms of gastroesophageal reflux disease (GERD), the GABA(B) receptor has been proposed as a therapeutic target for a number of diseases including GERD. Subsequently, there has been a significant effort to develop a peripherally-restricted GABA(B) agonist that is devoid of the central nervous system side effects that are... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=3797851 Thu, 29 Jul 2010 07:45:04 +0100 3797851 http://www.medworm.com/index.php?rid=3797849&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20655488%26dopt%3DAbstract Authors: Vlachou S, Markou A gamma-aminobutyric acid (GABA) is the predominant inhibitory neurotransmitter in the brain which acts through different receptor subtypes. Metabotropic GABA(B) receptors are widely distributed throughout the brain. Alterations in GABA signaling through pharmacological activation or deactivation of the GABA(B) receptor regulate behavior and brain reward processes. GABA(B) receptor agonists and, most recently, positive modulators have been found to inhibit the reinforcing effects of drugs of abuse, such as cocaine, amphetamine, nicotine, ethanol, and opiates. This converging evidence of the effects of GABA(B) compounds on the reinforcing properties of addictive drugs is based on behavioral studies that used a variety of procedures with relevance to reward pro... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=3797849 Thu, 29 Jul 2010 07:45:04 +0100 3797849 http://www.medworm.com/index.php?rid=3797848&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20655489%26dopt%3DAbstract Authors: Tyacke RJ, Lingford-Hughes A, Reed LJ, Nutt DJ The GABA(B) receptor plays an important role in the control of neurotransmitter release, and experiments using preclinical models have shown that modulation of this receptor can have profound effects on the reward process. This ability to affect the reward process has led to clinical investigations into the possibility that this could be a viable target in the treatment of addiction. Presented here is an overview of a number of studies testing this hypothesis in different drug dependencies. The studies reviewed have used the GABA(B) receptor agonist baclofen, which is currently the only GABA(B) agonist for use in humans. In addition, studies using the non-specific GABA(B) receptor agonists vigabatrin and tiagabine have been includ... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=3797848 Thu, 29 Jul 2010 07:45:04 +0100 3797848 http://www.medworm.com/index.php?rid=3797830&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20655490%26dopt%3DAbstract Authors: Cramer NP, Best TK, Stoffel M, Siarey RJ, Galdzicki Z Down syndrome (DS) results from the presence of an extra copy of genes on the long-arm of chromosome 21. Aberrant expression of these trisomic genes leads to widespread neurological changes that vary in their severity. However, how the presence of extra genes affects the physiological and behavioral phenotypes associated with DS is not well understood. The most likely cause of the complex DS phenotypes is the overexpression of dosage-sensitive genes. However, other factors, such as the complex interactions between gene products as proteins and noncoding RNAs, certainly play significant roles contributing to the spectrum of severity. Here we will review evidence regarding how the overexpression of one particular gene encodin... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=3797830 Thu, 29 Jul 2010 07:45:04 +0100 3797830 http://www.medworm.com/index.php?rid=3797822&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20655491%26dopt%3DAbstract Authors: Cryan JF, Slattery DA Dysfunction of the gamma amino butyric acid (GABA)-ergic system has been purported to play a role in psychiatric disorders, including anxiety and major depression. A clear link between GABA(A) receptors and anxiety has long been established. However, despite the GABA system being the prominent inhibitory neurotransmitter in the brain, a role in depression has been less well validated. GABA(B) receptors, first characterized by Bowery and colleagues 30 years ago, have been long postulated to be involved in the etiology of depression, but a lack of selective, orally active, pharmacological compounds slowed down their assessment. From the mid-1990s, more selective pharmacological and genetic tools for examining the GABA(B) system have provided greater insight... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=3797822 Thu, 29 Jul 2010 07:45:04 +0100 3797822 http://www.medworm.com/index.php?rid=3797805&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20655492%26dopt%3DAbstract Authors: Manev H, Dzitoyeva S Drosophila melanogaster, the "fruit fly," is being increasingly used as an experimental model in neurosciences, including neuropharmacology. The advantages of Drosophila over typical mammalian models in neuropharmacology include better access to genetic manipulation and the availability of almost unlimited numbers of experimental subjects at relatively low cost and with minimal regulatory restrictions. Nevertheless, one should remain cognizant of the substantial differences between insects and mammals. Insects, including Drosophila, utilize gamma-aminobutyric acid (GABA) as a neurotransmitter and express both ionotropic GABA receptors and metabotropic GABA-B receptors. Before cloning of the Drosophila GABA-B receptors (subunits 1-3), it had been assumed th... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=3797805 Thu, 29 Jul 2010 07:45:04 +0100 3797805 http://www.medworm.com/index.php?rid=3045296&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19945649%26dopt%3DAbstract Authors: Enna SJ PMID: 19945649 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=3045296 Wed, 02 Dec 2009 01:18:02 +0100 3045296 http://www.medworm.com/index.php?rid=2925139&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fsites%2Fentrez%3Fcmd%3DSearch%26db%3Dpubmed%26term%3D%28%2520%28%2522Adv%2520Pharmacol%2522%255Bta%255D%29%2520AND%2520%25222009%252F04%252F07%252012.30%2522%255BEDAT%255D%253A%25222009%252F10%252F25%252020.52%2522%255BEDAT%255D%29 855 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: "Adv Pharmacol"[ta] These pubmed results were generated on 2009/10/25PubMed, a service of the National Library of Medicine, includes over 15 million citations for biomedical articles back to the 1950's. These citations are from MEDLINE and additional life science journals. PubMed includes links to many sites providing full text articles and other related resources. (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=2925139 Mon, 26 Oct 2009 00:52:03 +0100 2925139 http://www.medworm.com/index.php?rid=1106107&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18086406%26dopt%3DAbstract Authors: Weiss RA PMID: 18086406 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=1106107 Thu, 20 Dec 2007 01:44:22 +0100 1106107 http://www.medworm.com/index.php?rid=1106106&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18086407%26dopt%3DAbstract Authors: Takebe Y, Uenishi R, Li X PMID: 18086407 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=1106106 Thu, 20 Dec 2007 01:44:20 +0100 1106106 http://www.medworm.com/index.php?rid=1106105&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18086408%26dopt%3DAbstract Authors: Murphy EM, Jimenez HR, Smith SM PMID: 18086408 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=1106105 Thu, 20 Dec 2007 01:44:19 +0100 1106105 http://www.medworm.com/index.php?rid=1106104&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18086409%26dopt%3DAbstract Authors: Harari A, Pantaleo G PMID: 18086409 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=1106104 Thu, 20 Dec 2007 01:44:17 +0100 1106104 http://www.medworm.com/index.php?rid=1106103&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18086410%26dopt%3DAbstract Authors: Strizki J PMID: 18086410 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=1106103 Thu, 20 Dec 2007 01:44:15 +0100 1106103 http://www.medworm.com/index.php?rid=1106102&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18086411%26dopt%3DAbstract Authors: Ilina T, Parniak MA PMID: 18086411 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=1106102 Thu, 20 Dec 2007 01:44:14 +0100 1106102 http://www.medworm.com/index.php?rid=1106101&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18086412%26dopt%3DAbstract Authors: Mitsuya H, Maeda K, Das D, Ghosh AK PMID: 18086412 [PubMed - as supplied by publisher] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=1106101 Thu, 20 Dec 2007 01:44:12 +0100 1106101 http://www.medworm.com/index.php?rid=1106100&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18086413%26dopt%3DAbstract Authors: Semenova EA, Marchand C, Pommier Y PMID: 18086413 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=1106100 Thu, 20 Dec 2007 01:44:11 +0100 1106100 http://www.medworm.com/index.php?rid=1106099&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18086414%26dopt%3DAbstract Authors: Turpin JA, Schito ML, Miller Jenkins LM, Inman JK, Appella E PMID: 18086414 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=1106099 Thu, 20 Dec 2007 01:44:09 +0100 1106099 http://www.medworm.com/index.php?rid=1106098&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18086415%26dopt%3DAbstract Authors: Quiñones-Mateu ME, Moore-Dudley DM, Jegede O, Weber J, J Arts E PMID: 18086415 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=1106098 Thu, 20 Dec 2007 01:44:07 +0100 1106098 http://www.medworm.com/index.php?rid=1106097&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18086416%26dopt%3DAbstract Authors: Giacca M PMID: 18086416 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=1106097 Thu, 20 Dec 2007 01:44:06 +0100 1106097 http://www.medworm.com/index.php?rid=1106096&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18086417%26dopt%3DAbstract Authors: Klase ZA, Duyne RV, Kashanchi F PMID: 18086417 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=1106096 Thu, 20 Dec 2007 01:44:04 +0100 1106096 http://www.medworm.com/index.php?rid=1106095&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18086418%26dopt%3DAbstract Authors: Dang Q, Hirsch VM PMID: 18086418 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=1106095 Thu, 20 Dec 2007 01:44:03 +0100 1106095 http://www.medworm.com/index.php?rid=1106094&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18086419%26dopt%3DAbstract Authors: Hoang V, Withers-Ward E, Camerini D PMID: 18086419 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=1106094 Thu, 20 Dec 2007 01:44:01 +0100 1106094 http://www.medworm.com/index.php?rid=1106093&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18086420%26dopt%3DAbstract Authors: Schiavone M, Quinto I, Scala G PMID: 18086420 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=1106093 Thu, 20 Dec 2007 01:44:00 +0100 1106093 http://www.medworm.com/index.php?rid=1106092&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18086421%26dopt%3DAbstract Authors: Ahmad N PMID: 18086421 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=1106092 Thu, 20 Dec 2007 01:43:58 +0100 1106092 http://www.medworm.com/index.php?rid=1106091&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18086422%26dopt%3DAbstract Authors: Angeletti PC, Zhang L, Wood C PMID: 18086422 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=1106091 Thu, 20 Dec 2007 01:43:56 +0100 1106091 http://www.medworm.com/index.php?rid=696702&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17586310%26dopt%3DAbstract Authors: Gallo RC PMID: 17586310 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=696702 Tue, 26 Jun 2007 18:13:20 +0100 696702 http://www.medworm.com/index.php?rid=696701&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17586311%26dopt%3DAbstract Authors: Lever AM PMID: 17586311 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=696701 Tue, 26 Jun 2007 18:13:20 +0100 696701 http://www.medworm.com/index.php?rid=696700&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17586312%26dopt%3DAbstract Authors: Prabakaran P, Dimitrov AS, Fouts TR, Dimitrov DS PMID: 17586312 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=696700 Tue, 26 Jun 2007 18:13:20 +0100 696700 http://www.medworm.com/index.php?rid=696699&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17586313%26dopt%3DAbstract Authors: Abbink TE, Berkhout B PMID: 17586313 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=696699 Tue, 26 Jun 2007 18:13:20 +0100 696699 http://www.medworm.com/index.php?rid=696698&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17586314%26dopt%3DAbstract Authors: Gatignol A PMID: 17586314 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=696698 Tue, 26 Jun 2007 18:13:20 +0100 696698 http://www.medworm.com/index.php?rid=696697&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17586315%26dopt%3DAbstract Authors: Felber BK, Zolotukhin AS, Pavlakis GN PMID: 17586315 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=696697 Tue, 26 Jun 2007 18:13:20 +0100 696697 http://www.medworm.com/index.php?rid=696696&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17586316%26dopt%3DAbstract Authors: Strebel K PMID: 17586316 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=696696 Tue, 26 Jun 2007 18:13:20 +0100 696696 http://www.medworm.com/index.php?rid=696695&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17586317%26dopt%3DAbstract Authors: Zhao RY, Elder RT, Bukrinsky M PMID: 17586317 [PubMed - as supplied by publisher] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=696695 Tue, 26 Jun 2007 18:13:20 +0100 696695 http://www.medworm.com/index.php?rid=696694&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17586318%26dopt%3DAbstract Authors: Louis JM, Ishima R, Torchia DA, Weber IT PMID: 17586318 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=696694 Tue, 26 Jun 2007 18:13:20 +0100 696694 http://www.medworm.com/index.php?rid=696693&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17586319%26dopt%3DAbstract Authors: Darlix JL, Garrido JL, Morellet N, Mély Y, Rocquigny H PMID: 17586319 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=696693 Tue, 26 Jun 2007 18:13:20 +0100 696693 http://www.medworm.com/index.php?rid=696692&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17586320%26dopt%3DAbstract Authors: Adamson CS, Freed EO PMID: 17586320 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=696692 Tue, 26 Jun 2007 18:13:20 +0100 696692 http://www.medworm.com/index.php?rid=696691&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17586321%26dopt%3DAbstract Authors: Foster JL, Garcia JV PMID: 17586321 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=696691 Tue, 26 Jun 2007 18:13:20 +0100 696691 http://www.medworm.com/index.php?rid=696690&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17586322%26dopt%3DAbstract Authors: Peterson S, Reid AP, Kim S, Siliciano RF PMID: 17586322 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=696690 Tue, 26 Jun 2007 18:13:20 +0100 696690 http://www.medworm.com/index.php?rid=696689&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17586323%26dopt%3DAbstract Authors: Yeung ML, Bennasser Y, Le SY, Jeang KT PMID: 17586323 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=696689 Tue, 26 Jun 2007 18:13:20 +0100 696689 http://www.medworm.com/index.php?rid=394023&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17175808%26dopt%3DAbstract Authors: Enna SJ, McCarson KE A great deal of effort has been expended in attempting to define the role of GABA in mediating the transmission and perception of pain. Pursuit of this question has been stimulated by the fact that GABAergic neurons are widely distributed throughout the central nervous system, including regions of the spinal cord dorsal horn known to be important for transmitting pain impulses to the brain. In addition, GABA neurons and receptors are found in supraspinal sites known to coordinate the perception and response to painful stimuli and this neurotransmitter system has been shown to regulate control of sensory information processing in the spinal cord. The discovery that GABA receptor agonists display antinociceptive properties in a variety of animal models of pa... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=394023 Sun, 01 Jan 2006 07:00:00 +0100 394023 http://www.medworm.com/index.php?rid=394022&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17175809%26dopt%3DAbstract Authors: Neto FL, Ferreira-Gomes J, Castro-Lopes JM PMID: 17175809 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=394022 Sun, 01 Jan 2006 07:00:00 +0100 394022 http://www.medworm.com/index.php?rid=394021&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17175810%26dopt%3DAbstract Authors: Krogsgaard-Larsen P, Frølund B, Liljefors T PMID: 17175810 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=394021 Sun, 01 Jan 2006 07:00:00 +0100 394021 http://www.medworm.com/index.php?rid=394020&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17175811%26dopt%3DAbstract Authors: Benes FM, Gisabella B PMID: 17175811 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=394020 Sun, 01 Jan 2006 07:00:00 +0100 394020 http://www.medworm.com/index.php?rid=394019&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17175812%26dopt%3DAbstract Authors: Costa E, Dong E, Grayson DR, Ruzicka WB, Simonini MV, Veldic M, Guidotti A PMID: 17175812 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=394019 Sun, 01 Jan 2006 07:00:00 +0100 394019 http://www.medworm.com/index.php?rid=394018&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17175813%26dopt%3DAbstract Authors: Roberts E PMID: 17175813 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=394018 Sun, 01 Jan 2006 07:00:00 +0100 394018 http://www.medworm.com/index.php?rid=394017&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17175814%26dopt%3DAbstract Authors: Macdonald RL, Kang JQ, Gallagher MJ, Feng HJ PMID: 17175814 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=394017 Sun, 01 Jan 2006 07:00:00 +0100 394017 http://www.medworm.com/index.php?rid=394016&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17175815%26dopt%3DAbstract Authors: Boehm SL, Ponomarev I, Blednov YA, Harris RA gamma-Aminobutyric acid A (GABA(A)) receptors are believed to mediate a number of alcohol's behavioral actions. Because the subunit composition of GABA(A) receptors determines receptor pharmacology, behavioral sensitivity to alcohol (ethanol) may depend on which subunits are present (or absent). A number of knockout and/or transgenic mouse models have been developed (alpha1, alpha2, alpha5, alpha6, beta2, beta3, gamma2S, gamma2L, delta) and tested for behavioral sensitivity to ethanol. Here we review the current GABA(A) receptor subunit knockout and transgenic literature for ethanol sensitivity, and integrate these results into those obtained using quantitative trait loci (QTL) analysis and gene expression assays. Converging evidenc... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=394016 Sun, 01 Jan 2006 07:00:00 +0100 394016 http://www.medworm.com/index.php?rid=394015&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17175816%26dopt%3DAbstract Authors: Koob GF PMID: 17175816 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=394015 Sun, 01 Jan 2006 07:00:00 +0100 394015 http://www.medworm.com/index.php?rid=394014&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17175817%26dopt%3DAbstract Authors: Sieghart W PMID: 17175817 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=394014 Sun, 01 Jan 2006 07:00:00 +0100 394014 http://www.medworm.com/index.php?rid=394013&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17175818%26dopt%3DAbstract Authors: Clausen RP, Madsen K, Larsson OM, Frølund B, Krogsgaard-Larsen P, Schousboe A PMID: 17175818 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=394013 Sun, 01 Jan 2006 07:00:00 +0100 394013 http://www.medworm.com/index.php?rid=394012&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17175819%26dopt%3DAbstract Authors: Johnston GA, Hanrahan JR, Chebib M, Duke RK, Mewett KN PMID: 17175819 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=394012 Sun, 01 Jan 2006 07:00:00 +0100 394012 http://www.medworm.com/index.php?rid=394011&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17239757%26dopt%3DAbstract Authors: PMID: 17239757 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=394011 Sun, 01 Jan 2006 07:00:00 +0100 394011 http://www.medworm.com/index.php?rid=394010&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17239758%26dopt%3DAbstract Authors: PMID: 17239758 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=394010 Sun, 01 Jan 2006 07:00:00 +0100 394010 http://www.medworm.com/index.php?rid=394009&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17239759%26dopt%3DAbstract Authors: Matsui F, Oohira A PMID: 17239759 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=394009 Sun, 01 Jan 2006 07:00:00 +0100 394009 http://www.medworm.com/index.php?rid=394008&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17239760%26dopt%3DAbstract Authors: Silva LC PMID: 17239760 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=394008 Sun, 01 Jan 2006 07:00:00 +0100 394008 http://www.medworm.com/index.php?rid=394007&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17239761%26dopt%3DAbstract Authors: Lamari FN, Karamanos NK PMID: 17239761 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=394007 Sun, 01 Jan 2006 07:00:00 +0100 394007 http://www.medworm.com/index.php?rid=394006&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17239762%26dopt%3DAbstract Authors: Mulloy B PMID: 17239762 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=394006 Sun, 01 Jan 2006 07:00:00 +0100 394006 http://www.medworm.com/index.php?rid=394005&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17239763%26dopt%3DAbstract Authors: Prabhakar V, Sasisekharan R PMID: 17239763 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=394005 Sun, 01 Jan 2006 07:00:00 +0100 394005 http://www.medworm.com/index.php?rid=394004&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17239764%26dopt%3DAbstract Authors: Pavão MS, Vilela-Silva AC, Mourão PA PMID: 17239764 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=394004 Sun, 01 Jan 2006 07:00:00 +0100 394004 http://www.medworm.com/index.php?rid=394003&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17239765%26dopt%3DAbstract Authors: Stylianou M, Triantaphyllidou IE, Vynios DH PMID: 17239765 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=394003 Sun, 01 Jan 2006 07:00:00 +0100 394003 http://www.medworm.com/index.php?rid=394002&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17239766%26dopt%3DAbstract Authors: Petit E, Delattre C, Papy-Garcia D, Michaud P PMID: 17239766 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=394002 Sun, 01 Jan 2006 07:00:00 +0100 394002 http://www.medworm.com/index.php?rid=394001&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17239767%26dopt%3DAbstract Authors: Linhardt RJ, Avci FY, Toida T, Kim YS, Cygler M PMID: 17239767 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=394001 Sun, 01 Jan 2006 07:00:00 +0100 394001 http://www.medworm.com/index.php?rid=394000&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17239768%26dopt%3DAbstract Authors: Handley CJ, Samiric T, Ilic MZ PMID: 17239768 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=394000 Sun, 01 Jan 2006 07:00:00 +0100 394000 http://www.medworm.com/index.php?rid=393999&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17239769%26dopt%3DAbstract Authors: Sampaio LO, Nader HB PMID: 17239769 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=393999 Sun, 01 Jan 2006 07:00:00 +0100 393999 http://www.medworm.com/index.php?rid=393998&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17239770%26dopt%3DAbstract Authors: Nandini CD, Sugahara K PMID: 17239770 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=393998 Sun, 01 Jan 2006 07:00:00 +0100 393998 http://www.medworm.com/index.php?rid=393997&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17239771%26dopt%3DAbstract Authors: Theocharis AD, Tsolakis I, Tzanakakis GN, Karamanos NK PMID: 17239771 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=393997 Sun, 01 Jan 2006 07:00:00 +0100 393997 http://www.medworm.com/index.php?rid=393996&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17239772%26dopt%3DAbstract Authors: Wegrowski Y, Maquart FX PMID: 17239772 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=393996 Sun, 01 Jan 2006 07:00:00 +0100 393996 http://www.medworm.com/index.php?rid=393995&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17239773%26dopt%3DAbstract Authors: Aono S, Oohira A PMID: 17239773 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=393995 Sun, 01 Jan 2006 07:00:00 +0100 393995 http://www.medworm.com/index.php?rid=393994&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17239774%26dopt%3DAbstract Authors: Rauch U, Kappler J PMID: 17239774 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=393994 Sun, 01 Jan 2006 07:00:00 +0100 393994 http://www.medworm.com/index.php?rid=393993&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17239775%26dopt%3DAbstract Authors: Rolls A, Schwartz M PMID: 17239775 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=393993 Sun, 01 Jan 2006 07:00:00 +0100 393993 http://www.medworm.com/index.php?rid=393992&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17239776%26dopt%3DAbstract Authors: Gowda DC PMID: 17239776 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=393992 Sun, 01 Jan 2006 07:00:00 +0100 393992 http://www.medworm.com/index.php?rid=393991&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17239777%26dopt%3DAbstract Authors: Toida T, Sakai S, Akiyama H, Linhardt RJ PMID: 17239777 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=393991 Sun, 01 Jan 2006 07:00:00 +0100 393991 http://www.medworm.com/index.php?rid=393990&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17239778%26dopt%3DAbstract Authors: Campo GM, Avenoso A, Campo S, Ferlazzo AM, Calatroni A PMID: 17239778 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=393990 Sun, 01 Jan 2006 07:00:00 +0100 393990 http://www.medworm.com/index.php?rid=393988&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17239779%26dopt%3DAbstract Authors: Brandl N, Holzmann J, Schabus R, Huettinger M PMID: 17239779 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=393988 Sun, 01 Jan 2006 07:00:00 +0100 393988 http://www.medworm.com/index.php?rid=393986&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17239780%26dopt%3DAbstract Authors: Fioravanti A, Collodel G PMID: 17239780 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=393986 Sun, 01 Jan 2006 07:00:00 +0100 393986 http://www.medworm.com/index.php?rid=393984&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17239781%26dopt%3DAbstract Authors: Dobenecker B PMID: 17239781 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=393984 Sun, 01 Jan 2006 07:00:00 +0100 393984 http://www.medworm.com/index.php?rid=393982&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17239782%26dopt%3DAbstract Authors: Uebelhart D, Knols R, de Bruin ED, Verbruggen G PMID: 17239782 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=393982 Sun, 01 Jan 2006 07:00:00 +0100 393982 http://www.medworm.com/index.php?rid=393980&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17239783%26dopt%3DAbstract Authors: Verbruggen G PMID: 17239783 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=393980 Sun, 01 Jan 2006 07:00:00 +0100 393980 http://www.medworm.com/index.php?rid=393978&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17239784%26dopt%3DAbstract Authors: Bana G, Jamard B, Verrouil E, Mazières B PMID: 17239784 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=393978 Sun, 01 Jan 2006 07:00:00 +0100 393978 http://www.medworm.com/index.php?rid=393976&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D17239785%26dopt%3DAbstract Authors: Uebelhart D, Knols R, de Bruin ED, Verbruggen G PMID: 17239785 [PubMed - in process] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=393976 Sun, 01 Jan 2006 07:00:00 +0100 393976 http://www.medworm.com/index.php?rid=394041&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16492538%26dopt%3DAbstract Authors: Young A PMID: 16492538 [PubMed - indexed for MEDLINE] (Source: Advances in Pharmacology) Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=394041 Sat, 01 Jan 2005 07:00:00 +0100 394041 http://www.medworm.com/index.php?rid=394040&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16492539%26dopt%3DAbstract Authors: Young A Amylin and insulin are co-localized within the same secretory granules of pancreatic beta-cells. Acutely, the secreted ratio of amylin:insulin is comparatively invariant, but long-standing hyperglycemia may favor induction of amylin synthesis and secretion over that of insulin. Amylin is also found in much lesser quantities in the gut and other tissues. In humans, both type 1 diabetes mellitus and the later stages of type 2 diabetes mellitus are characterized by deficiency of both insulin and amylin secretion. The severity of amylin deficiency appears to correlate with the severity of insulin deficiency. This concordance of deficiencies in amylin and insulin secretion observed with the progression of diabetes mellitus is consistent with their co-localization in pancrea... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=394040 Sat, 01 Jan 2005 07:00:00 +0100 394040 http://www.medworm.com/index.php?rid=394039&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16492540%26dopt%3DAbstract Authors: Young A Despite clear evidence for a distinct amylin pharmacology and localization of such pharmacology to sites such as the nucleus accumbens,efforts to clone an amylin receptor were fruitless for over a decade. This enigma led many to doubt the status of amylin as a bona fide hormone.Yet it became apparent during those cloning efforts that, whatever the amylin receptor was, it was somehow similar to a calcitonin receptor. The enigma of the amylin receptor was solved following the identification of receptor activity modifying proteins (RAMPs). These single transmembrane spanning molecules, when associated with a calcitonin receptor, altered its pharmacology from calcitonin-preferring to amylin-preferring. With at least two forms of the calcitonin receptor and three forms of R... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=394039 Sat, 01 Jan 2005 07:00:00 +0100 394039 http://www.medworm.com/index.php?rid=394038&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16492541%26dopt%3DAbstract Authors: Young A The most potent actions of amylin that occur at physiological plasma concentrations include inhibition of food intake, gastric emptying, acid and digestive enzyme secretion, and glucagon secretion. These actions share a common outcome; they each help regulate the rate at which nutrients (including glucose) appear in the blood (Ra). Amylin physiologically orchestrates, via several parallel processes, the rate of entry of nutrient into the circulation, as shown schematically in Fig. 1. In this way, amylin's function may be viewed as complementary to that of insulin (secreted from the same pancreatic beta-cells), which orchestrates the exit of nutrient from blood and its storage in peripheral tissues. The following discussion addresses the emerging picture that, although ... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=394038 Sat, 01 Jan 2005 07:00:00 +0100 394038 http://www.medworm.com/index.php?rid=394037&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16492542%26dopt%3DAbstract Authors: Young A Over 100 publications, principally from five groups, describe an effect of amylin and amylin analogs in inhibition of food intake in animals and humans. The major groups contributing to this area are those of the following: Chance and Balasubramaniam (Balasubramaniam et al., 1991a,b; Chance et al., 1991a,b, 1992a,b, 1993). Morley, Flood, and Edwards (Edwards and Morley, 1992; Flood and Morley, 1992; Macintosh et al., 2000; Morley and Flood, 1991, 1994; Morley et al., 1992, 1993, 1994, 1995, 1996, 1997). Lutz, Geary, and others (Barth et al., 2003; Del Prete et al., 2002; Lutz et al., 1994, 1995a,b, 1996a,b, 1997a,b, 1998a,b,c, 2000a,b, 2001a,b,c, 2003; Mollet et al., 2001, 2003a,b, 2004; Riediger et al., 2002, 2004; Rushing et al., 2000a,b, 2001, 2002). Workers at Amyl... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=394037 Sat, 01 Jan 2005 07:00:00 +0100 394037 http://www.medworm.com/index.php?rid=394036&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16492543%26dopt%3DAbstract Authors: Young A In studies aimed at defining the role of amylin in glucose control, elevations of postprandial glucose concentration were blunted in subjects infused with the human amylin analog, pramlintide (Kolterman et al., 1995, 1996). An effect similar to blunt glucose excursions was observed by Brown and others during infusions of amylin in dogs trained to drink glucose (Brown et al., 1994). The effect of pramlintide in humans was present when glucose was administered orally, but not when administered intravenously, suggesting that the effect was due to a deceleration of glucose uptake from the meal, rather than an acceleration of its metabolism (Kolterman et al., 1995). Since amylin did not affect the rate of glucose transit across exteriorized gut loops (Young and Gedulin, 200... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=394036 Sat, 01 Jan 2005 07:00:00 +0100 394036 http://www.medworm.com/index.php?rid=394035&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16492544%26dopt%3DAbstract Authors: Young A Rat amylin subcutaneously injected into rats dose-dependently inhibits pentagastrin-stimulated gastric acid secretion and protects the stomach from ethanol-induced gastritis. The ED50s for these actions (0.050 and 0.036 microg, respectively) are the lowest for any dose-dependent effect of amylin thus far described, and their similar potencies are consistent with a mechanistic (causal) association. At higher amylin doses, inhibition of gastric acid secretion was almost complete (93.4%). Gastric injury (measured by a subjective analog scale) was inhibited by up to 67%. The observation that effective doses of amylin result in plasma concentrations of 7-10 pM (i.e., within the reported range; Pieber et al., 1994) supports the interpretation that inhibition of gastric acid ... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=394035 Sat, 01 Jan 2005 07:00:00 +0100 394035 http://www.medworm.com/index.php?rid=394034&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16492545%26dopt%3DAbstract Authors: Young A This chapter describes a physiological and profound effect of amylin to inhibit meal-related glucagon secretion. Glucagon is processed from a large precursor, proglucagon, in a tissue-specific manner in pancreatic alpha-cells. In addition to amino acid nutrient stimuli, glucagon is also secreted in response to stressful stimuli, such as hypoglycemia and hypovolemia. Glucagon primarily acts on liver to initiate glycogenolysis and gluconeogenesis, resulting in a rapid increase in endogenous production of glucose. With longer stimulation, glucagon action at the liver results in a glucose-sparing activation of free fatty acid oxidation and production of ketones. During hypoglycemia, glucagon secretion is clearly a protective feed-back, defending the organism against damagi... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=394034 Sat, 01 Jan 2005 07:00:00 +0100 394034 http://www.medworm.com/index.php?rid=394033&cid=s_34429_13_f&fid=34429&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D16492546%26dopt%3DAbstract Authors: Young A Reports of the effects of amylin and amylin agonists on insulin secretion have varied widely. Some confusion can be attributed to the use of human amylin, which has been shown to readily fall out of solution resulting in low estimates of bioactivity. Some confusion can be resolved by assessing the probability that this had happened. The view taken here, supported by authors using reliable and well-characterized ligands (representing the preponderance of recent studies), is that exogenously administered amylin agonists inhibit insulin secretion, at least partly via activation of an amylin-like receptor linked to Gi-mediated inhibition of cAMP in islets. There may additionally be autonomic extrapancreatic effects of amylin on insulin secretion that derive from its action... Advances in Pharmacology journals http://www.medworm.com/rss/comments.php?id=394033 Sat, 01 Jan 2005 07:00:00 +0100 394033