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 'British Journal of Pharmacology' source. Wed, 08 Feb 2012 14:04:03 +0100 http://www.medworm.com/index.php?rid=5648074&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01886.x Conclusions and Implications.  The NaHS/H2S‐induced mechanical hyperalgesia and allodynia thus require activation of both Cav3.2 and TRPA1 channels in mice.© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5648074 Thu, 02 Feb 2012 05:00:00 +0100 5648074 http://www.medworm.com/index.php?rid=5648073&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01885.x Conclusions and Implications.  We have identified that TGF‐β impairs glucocorticoid responses in the A549 and BEAS‐2B cell lines.© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5648073 Thu, 02 Feb 2012 05:00:00 +0100 5648073 http://www.medworm.com/index.php?rid=5648072&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01878.x Conclusions and Implications.  These studies demonstrated that chronic administration of JNJ‐26070109 effectively inhibited gastric acid secretion and suppressed proton pump inhibitor (PPI)‐induced acid rebound in the rat. This work advances the field by demonstrating that modest doses of a competitive CCK2 receptor antagonist have significant and functionally important anti‐trophic actions in the gastric mucosa. These properties make JNJ‐26070109 is a suitable candidate for clinical investigation for the treatment of GORD.© Janssen Research and Development LLC British Journal of Pharmacology © The British Pharmacological Society (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5648072 Thu, 02 Feb 2012 05:00:00 +0100 5648072 http://www.medworm.com/index.php?rid=5648071&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01887.x Conclusions and Implications.  Curcumin can be used to investigate impact of BCRP on oral bioavailability of drugs in humans. Besides the limited dissolution, OATP2B1 saturation is suggested as a mechanism underlying the non‐linearity in the dose‐exposure relationship of sulfasalazine.© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5648071 Thu, 02 Feb 2012 05:00:00 +0100 5648071 http://www.medworm.com/index.php?rid=5648070&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01879.x Conclusions and Implications.  Cannabichromene selectively reduces inflammation‐induced hypermotility in vivo in a cannabinoid receptor‐ and TRPA1‐independent manner.© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5648070 Thu, 02 Feb 2012 05:00:00 +0100 5648070 http://www.medworm.com/index.php?rid=5648069&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01880.x Conclusion:  Our data suggest 1). the induction of non‐TdP‐like VT/VF, which is caused by slowing of conduction via blockade of INa (like Class Ic flecainide), may constitute a more important risk for terfenadine‐induced cardiac death, 2). although terfenadine is a potent hERG blocker, the risk for non‐TdP‐like VT/VF exceeds the risk for TdPs, 3). the role of cardiac wavelength could serve as a biomarker for terfenadine‐induced VT/VF.© Janssen Pharmaceutica NV British Journal of Pharmacology © The British Pharmacological Society (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5648069 Thu, 02 Feb 2012 05:00:00 +0100 5648069 http://www.medworm.com/index.php?rid=5648068&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01882.x Conclusions:  EPA‐FFA inhibits MC‐26 CRC cell liver metastasis. EPA incorporation is associated with a ‘PGE2 to PGE3 switch’ in liver tumours. Inhibition of PGE2‐EP4 receptor‐dependent CRC cell motility likely contributes to the anti‐neoplastic activity of EPA.© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5648068 Thu, 02 Feb 2012 05:00:00 +0100 5648068 http://www.medworm.com/index.php?rid=5648067&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01881.x Conclusions and Implications.  From the present radioligand binding approach with intact tissue segments, we constructed a distribution map of mAChRs and β‐adrenoceptors in human bronchus and lung parenchyma for the first time, providing important evidence for future pharmacotherapy and new drug development for respiratory disorders.© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5648067 Thu, 02 Feb 2012 05:00:00 +0100 5648067 http://www.medworm.com/index.php?rid=5648066&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01883.x Conclusions and Implications.  The presence of luminal ACh and activation of transepithelial ion currents by luminal ACh receptors identifies a novel non‐neuronal cholinergic pathway in the airway lining fluid. This pathway could represent a novel drug target in the airways.© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5648066 Thu, 02 Feb 2012 05:00:00 +0100 5648066 http://www.medworm.com/index.php?rid=5667355&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01888.x Conclusions and Implications.  This is the first report of hyperphagia induced by acute noladin administration, and the first description of behavioural actions in rats. Consistent with prevailing notions about the role of endocannabinoids in appetite, a hyperphagic dose of noladin markedly increased the effort expended by animals to obtain food. Thus, noladin exerts a specific action on eating motivation; possibly promoting eating by increasing the incentive value of food.© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5667355 Wed, 01 Feb 2012 05:00:00 +0100 5667355 http://www.medworm.com/index.php?rid=5648065&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01884.x Conclusions and Implications.  Overall, we found a novel sensory TRP acting metabolite and suggest that its use may help to better understand TRPV4 physiology in nociception and the associated inflammation mechanisms.© 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5648065 Wed, 01 Feb 2012 05:00:00 +0100 5648065 http://www.medworm.com/index.php?rid=5648082&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01870.x Conclusions and Implications.  These data document an antidote‐like effect of NMDPEF against PQ‐induced toxicity in vitro and in vivo and suggest a key role for QR2 in the regulation of oxidative stress. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5648082 Tue, 31 Jan 2012 05:00:00 +0100 5648082 http://www.medworm.com/index.php?rid=5648081&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01871.x This article, written by members of the NC‐IUPHAR subcommittee on receptors for VIP and PACAP, confirms the existing nomenclature for these receptors and reviews our current understanding of their structure, pharmacology and functions and their likely physiological roles in health and disease. More detailed information has been incorporated into newly revised pages in the IUPHAR database (http://iuphar‐db.org/DATABASE/FamilyMenuForward?familyId=67). (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5648081 Tue, 31 Jan 2012 05:00:00 +0100 5648081 http://www.medworm.com/index.php?rid=5648080&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01872.x Conclusions and Implications.  Taken together, our data demonstrate that NPY delays the acquisition, reduces the expression of conditioned fear while promoting fear extinction. Although these effects appear to be primarily mediated by Y1 receptors, the pronounced phenotype of Y1Y2 double KO mice suggests a synergistic role of Y2 receptors both in fear acquisition and in fear extinction. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5648080 Tue, 31 Jan 2012 05:00:00 +0100 5648080 http://www.medworm.com/index.php?rid=5648079&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01874.x Conclusions and Implications:  Based on the nonclinical and clinical cardiovascular safety assessment, JNJ‐Q2 has a safe cardiovascular profile for administration in humans with comparable or reduced potential to prolong the QT interval compared to moxifloxacin. The results demonstrate the importance of compensatory sodium and calcium channel activity in offsetting potassium channel activity for compounds with a fluoroquinolone core. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5648079 Tue, 31 Jan 2012 05:00:00 +0100 5648079 http://www.medworm.com/index.php?rid=5648078&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01873.x SummaryThe incidence of human malignant pleural mesothelioma (hMPM) is still increasing worldwide. hMPM prognosis is poor even if the median survival time has been slightly improved after the introduction of the up‐to‐date chemotherapy. Nevertheless, large phase II/III trials support the combination of platinum‐derivatives and pemetrexed or raltitrexed, as preferred first‐line schedule. Better understanding of the molecular machinery of hMPM will lead to the design and synthesis of novel compounds targeted against pathways identified as crucial for hMPM cell proliferation and spreading. Among them, several receptors tyrosine kinase show altered activity in subsets of hMPM. This observation suggests that these kinases might represent novel therapeutic targets in this chemotherapy‐... British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5648078 Tue, 31 Jan 2012 05:00:00 +0100 5648078 http://www.medworm.com/index.php?rid=5648077&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01875.x Conclusions and Implications:  We document the molecular mechanisms underlying the coupling of human HCA3 to the ERK1/2 MAP kinase pathway in CHO‐K1 and A431 cells, which implicate the Gi protein‐initiated, PLC/PKC‐ and PDGFR/EGFR transactivation‐dependent pathways. These observations may provide new insights into the pharmacological effects and the physiological functions modulated by the HCA3‐mediated activation of ERK1/2. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5648077 Tue, 31 Jan 2012 05:00:00 +0100 5648077 http://www.medworm.com/index.php?rid=5648076&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01876.x Conclusions and Implications.  Arginase II removal prevents nitrate tolerance. This may be due to decreased uncoupling of eNOS and the subsequent ROS production following arginase II removal. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5648076 Tue, 31 Jan 2012 05:00:00 +0100 5648076 http://www.medworm.com/index.php?rid=5648075&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01877.x Conclusions and Implications.  Resveratrol exerts cardioprotection by reducing ROS and preserving mitochondrial function. The PKC‐α‐dependent inhibition of NHE and subsequent attenuation of [Ca2+]i overload may be a cardioprotective mechanism. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5648075 Tue, 31 Jan 2012 05:00:00 +0100 5648075 http://www.medworm.com/index.php?rid=5628823&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01628.x CONCLUSIONS AND IMPLICATIONS Partial α4β2 agonists induced relatively enhanced effects on the firing rate of dopaminergic neurons, and the effect was mainly attributed to the existence of native α4β2* receptor reserve. The results have implications in the understanding of physiological effects and therapeutic efficacies of α4β2 partial agonists. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5628823 Thu, 26 Jan 2012 18:51:34 +0100 5628823 http://www.medworm.com/index.php?rid=5628822&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01625.x CONCLUSIONS AND IMPLICATIONS The opposing behavioural and molecular changes observed after chronic treatment with AM630 or JWH133 support the key role of CB2 receptors in the regulation of anxiety. Indeed, the efficacy of AM630 in reducing the anxiety of the spontaneously anxious DBA/2 strain of mice strengthens the potential of the CB2 receptor as a new target in the treatment of anxiety‐related disorders. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5628822 Thu, 26 Jan 2012 18:51:28 +0100 5628822 http://www.medworm.com/index.php?rid=5628821&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01617.x CONCLUSIONS AND IMPLICATIONS Mesenteric I/R potentiated the ET‐1‐mediated vasoconstriction by a mechanism that involves up‐regulation of muscular ETB receptors and decrease in NO bioavailability. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5628821 Thu, 26 Jan 2012 18:51:27 +0100 5628821 http://www.medworm.com/index.php?rid=5628820&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01596.x CONCLUSIONS AND IMPLICATIONS Our electrophysiological recordings of pure α7 nAChR currents elicited by rapid application of agonists demonstrated that functional α7 nAChRs are expressed and contribute to depolarization‐elicited exocytosis in human chromaffin cells. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5628820 Thu, 26 Jan 2012 18:51:23 +0100 5628820 http://www.medworm.com/index.php?rid=5628819&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01602.x CONCLUSIONS AND IMPLICATIONS Vulnerability to stress might constitute a risk factor for the development of AD, and pharmacological treatment with venlafaxine may represent a therapeutic strategy for the treatment of stress‐related disorders, including AD. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5628819 Thu, 26 Jan 2012 18:51:22 +0100 5628819 http://www.medworm.com/index.php?rid=5628818&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01541.x CONCLUSIONS AND IMPLICATIONS Br‐DIF‐1 accelerated the differentiation, induced by 1% DMSO, of P19CL6 cells into spontaneously beating cardiomyocyte‐like cells, partly by enhancing the expression of the T‐type Ca2+ channel gene. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5628818 Thu, 26 Jan 2012 18:51:19 +0100 5628818 http://www.medworm.com/index.php?rid=5628817&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01736.x (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5628817 Thu, 26 Jan 2012 18:51:06 +0100 5628817 http://www.medworm.com/index.php?rid=5628816&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01737.x (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5628816 Thu, 26 Jan 2012 18:51:05 +0100 5628816 http://www.medworm.com/index.php?rid=5628815&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01735.x (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5628815 Thu, 26 Jan 2012 18:51:03 +0100 5628815 http://www.medworm.com/index.php?rid=5609057&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01869.x Conclusions and Implications.  Both triterpenes restricted the development of the characteristic hallmarks of EAE. We envision these natural products as novel helpful tools for intervention in autoimmune and neurodegenerative diseases including MS. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5609057 Fri, 20 Jan 2012 18:19:54 +0100 5609057 http://www.medworm.com/index.php?rid=5609058&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01868.x Conclusions and Implications.  These observations should help predict the clinical effects of 5‐HT1E‐selective drugs. For example, we have confirmed a functional link between the stimulation of 5‐HT1E receptors and the inhibition of adenylate cyclase activity in the dentate gyrus; this suggests 5‐HT1E receptors may mediate serotonin's regulation of hippocampal activity, making it a possible drug target for the treatment of neuropsychiatric disorders characterized by memory deficits (e.g. Alzheimer's disease) or as a target for the treatment of temporal lobe epilepsy. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5609058 Fri, 20 Jan 2012 05:00:00 +0100 5609058 http://www.medworm.com/index.php?rid=5597925&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01867.x Conclusions and Implications.  It is concluded that 5‐HT is able to induce a large contraction in rabbit autologous jugular‐vein grafts through (i) an increased number of differentiated contractile SMCs, (ii) an increased number of SMCs expressing contractile 5‐HT2A‐ and 5‐HT1B/1D‐receptors and (iii) a down‐regulation of the function of the relaxant SMC 5‐HT7 receptors. These changes in the vein‐graft may help it to resist the higher pressure present on the arterial side of the circulation. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5597925 Tue, 17 Jan 2012 18:52:57 +0100 5597925 http://www.medworm.com/index.php?rid=5597936&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01856.x Conclusions and Implications.  Particular natural polyamines prevented OVX‐induced bone loss through a mechanism related to the disturbance of differentiation and maturation of osteoclasts rather than osteoblasts. Our results suggest that supplementation of particular natural polyamines would be beneficial for the prophylaxis as well as the therapy of metabolic bone diseases such as postmenopausal osteoporosis. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5597936 Tue, 17 Jan 2012 05:00:00 +0100 5597936 http://www.medworm.com/index.php?rid=5597935&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01858.x Conclusions and Implications.  The present study demonstrates that P‐gp inhibition can enhance intracerebral imipramine concentrations, thus supporting the hypothesis that P‐gp restricts brain levels of certain antidepressants, including imipramine. These findings may help to explain reports of a beneficial response to adjunctive therapy with verapamil in TRD. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5597935 Tue, 17 Jan 2012 05:00:00 +0100 5597935 http://www.medworm.com/index.php?rid=5597934&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01857.x This article will cover the recent advances in BM‐derived cell‐based therapy and implication of CD31+ cells (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5597934 Tue, 17 Jan 2012 05:00:00 +0100 5597934 http://www.medworm.com/index.php?rid=5597933&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01859.x AbstractTo establish the druggability of a target, genetic validation needs to be supplemented with pharmacological validation. Pharmacological studies, especially in the kinase field, are hampered by the fact that many reference inhibitors are not fully selective for one target. Fortunately, the initial trickle of selective inhibitors released in the public domain has steadily swelled into a stream. However, rationally picking the most selective tool compound out of the increasing amounts of available inhibitors, has become progressively difficult due to the lack of accurate quantitative descriptors of drug selectivity. A recently published approach, termed ‘selectivity entropy’ is an improved way of expressing selectivity as a single‐value parameter and enables rank‐ordering of i... British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5597933 Tue, 17 Jan 2012 05:00:00 +0100 5597933 http://www.medworm.com/index.php?rid=5597932&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01861.x Conclusions and Implications.  Bradykinin‐mediated inflammatory responses to intra‐articular carrageenan were not controlled by steroids, which were not capable of preventing bradykinin effects either by direct activation of the B2 receptor, or through the indirect effects mediated by the release of eicosanoids and cytokines. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5597932 Tue, 17 Jan 2012 05:00:00 +0100 5597932 http://www.medworm.com/index.php?rid=5597931&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01860.x Conclusions and Implications.  Whilst glucocorticoids activate SGK1 and increase the surface abundance of α‐, β‐ and γ‐ENaC, these responses are transient and cannot account for the sustained activation of ENaC. The maintenance of ENaC activity does, however, depend upon SGK1 and this protein kinase must therefore play an important but permissive role in glucocorticoid induced ENaC activation. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5597931 Tue, 17 Jan 2012 05:00:00 +0100 5597931 http://www.medworm.com/index.php?rid=5597930&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01862.x Conclusions and Implications.  Each molecule of balanocarpol may bind at least two sphingosine kinase 1 catalytic molecules to reduce the activity of each simultaneously. These findings suggest that resveratrol, ampelopsin A and balanocarpol perturb sphingosine kinase 1‐mediated signalling and which might provide an explanation for their anti‐cancer activity. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5597930 Tue, 17 Jan 2012 05:00:00 +0100 5597930 http://www.medworm.com/index.php?rid=5597929&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01863.x Conclusions and Implications.  In contrast to previous assumptions, Kv7.1 channels expressed in arterial myocytes are functional ion channels. Although these channels do not appear to contribute to resting vascular tone, Kv7.1 activators were effective vasorelaxants. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5597929 Tue, 17 Jan 2012 05:00:00 +0100 5597929 http://www.medworm.com/index.php?rid=5597928&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01864.x Conclusions and Implications.  FM reversed oxidative stress‐induced corticosteroid insensitivity and decreased β2 receptor dependent cAMP production via inhibition of PI3Kδ signalling. A combination of a corticosteroid with FM will be more effective than that with SM under conditions of high oxidative stress, such as in COPD. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5597928 Tue, 17 Jan 2012 05:00:00 +0100 5597928 http://www.medworm.com/index.php?rid=5597927&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01865.x Conclusions and Implications.  These data demonstrate that FTY720 increases vascular tone and blood pressure only in hypertensive rats, most likely due to its sphingosine kinase inhibitory effect. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5597927 Tue, 17 Jan 2012 05:00:00 +0100 5597927 http://www.medworm.com/index.php?rid=5597926&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01866.x Conclusions and Implications.  These results demonstrate that PI3Kγ is essential to MCP‐1‐stimulated aortic SMC migration and amplifies cell migration induced by PDGF by an autocrine/paracrine loop involving MCP‐1 secretion and CCR2 activation and suggest a role of this enzyme in aortic fibroproliferative pathologies. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5597926 Tue, 17 Jan 2012 05:00:00 +0100 5597926 http://www.medworm.com/index.php?rid=5582040&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01605.x CONCLUSIONS AND IMPLICATIONS Our data reveal that tryptanthrin is a potent natural inhibitor of cellular LT biosynthesis with proven efficacy in whole blood and is effective in vivo after oral administration. Its unique pharmacological profile supports further analysis to exploit its pharmacological potential. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5582040 Fri, 13 Jan 2012 23:18:45 +0100 5582040 http://www.medworm.com/index.php?rid=5582039&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01607.x CONCLUSIONS AND IMPLICATIONS Pyridoxine mitigated eNOS uncoupling induced by ox‐LDL. This protectant effect was related to phosphorylation of eNOS Thr495 stimulated by PKCα, not via NADPH oxidase. These results provide support for the use of pyridoxine in ox‐LDL‐related vascular endothelial dysfunction. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5582039 Fri, 13 Jan 2012 23:18:43 +0100 5582039 http://www.medworm.com/index.php?rid=5582038&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01603.x CONCLUSIONS AND IMPLICATIONS Cardamonin potentiates TRAIL‐induced apoptosis through ROS‐CHOP‐mediated up‐regulation of DRs, decreased expression of decoy receptor and cell survival proteins. Thus, cardamonin has the potential to make TRAIL more effective as an anticancer therapy. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5582038 Fri, 13 Jan 2012 23:18:42 +0100 5582038 http://www.medworm.com/index.php?rid=5582037&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01598.x CONCLUSIONS AND IMPLICATIONS DS exerts intestinal anti‐inflammatory activity in different rodent models of colitis through down‐regulation of IL‐17 expression. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5582037 Fri, 13 Jan 2012 23:18:40 +0100 5582037 http://www.medworm.com/index.php?rid=5582036&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01583.x CONCLUSIONS AND IMPLICATIONS Our data suggest that increased activity of MMP‐2 in FHRs impairs endothelial function and promotes hypertension. Inhibition of MMP‐2 could be a potential therapeutic strategy for the management of hypertension. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5582036 Fri, 13 Jan 2012 23:18:37 +0100 5582036 http://www.medworm.com/index.php?rid=5582035&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01582.x CONCLUSIONS AND IMPLICATIONS These findings suggest that morphine has two sites of action, a low‐affinity, competitive site and a high‐affinity, non‐competitive site that is not available when the channel is activated. The affinity of morphine for the latter is reduced by the 5‐HT3B subunit. Our results reveal that morphine causes a high‐affinity, insurmountable and subunit‐dependent inhibition of human 5‐HT3 receptors. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5582035 Fri, 13 Jan 2012 23:18:35 +0100 5582035 http://www.medworm.com/index.php?rid=5582034&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01568.x CONCLUSIONS AND IMPLICATIONS 17R‐RvD1 is a novel natural inhibitory substance specific for TRPV3. The results of our behavioural studies suggest that 17R‐RvD1 has acute analgesic potential via TRPV3‐specific mechanisms. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5582034 Fri, 13 Jan 2012 23:18:33 +0100 5582034 http://www.medworm.com/index.php?rid=5582033&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01472.x This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue‐3 (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5582033 Fri, 13 Jan 2012 23:18:22 +0100 5582033 http://www.medworm.com/index.php?rid=5582032&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01606.x This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue‐3 (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5582032 Fri, 13 Jan 2012 23:18:16 +0100 5582032 http://www.medworm.com/index.php?rid=5582031&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01788.x (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5582031 Fri, 13 Jan 2012 23:18:15 +0100 5582031 http://www.medworm.com/index.php?rid=5582017&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01855.x Conclusions and Implications.  This study reveals a tight overlap in the pharmacological profiles of TRPM7 and SK channels. NS8593 acts as a negative gating modulator of TRPM7 and is well suited to study functional features and cellular roles of endogenous TRPM7. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5582017 Fri, 13 Jan 2012 23:10:51 +0100 5582017 http://www.medworm.com/index.php?rid=5582019&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01853.x Conclusions and Implications.  MATE1 dysfunction caused a remarkable elevation of the metformin concentration in the liver and led to lactic acidosis, suggesting that the homozygous MATE1 variant could be one of the risk factors for metformin‐induced lactic acidosis. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5582019 Fri, 13 Jan 2012 05:00:00 +0100 5582019 http://www.medworm.com/index.php?rid=5582018&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01854.x Conclusions and Implications.  These results suggest that the novel compound C66 is a potential anti‐inflammatory agent and might be beneficial for the prevention of diabetic nephropathy. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5582018 Fri, 13 Jan 2012 05:00:00 +0100 5582018 http://www.medworm.com/index.php?rid=5582026&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01846.x Conclusions and implications  The results suggest that the PREP may play a role in brain accumulation and aggregation of α‐syn, while KYP‐2047 seems to effectively prevent these processes. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5582026 Tue, 10 Jan 2012 05:00:00 +0100 5582026 http://www.medworm.com/index.php?rid=5582025&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01847.x AbstractFibrosis, the result of excess deposition of extracellular matrix (ECM), in particular collagen, leads to scarring and loss of function in tissues that include the heart, lung, kidney and liver. The second messenger cyclic AMP (cAMP) can inhibit the formation and extent of ECM during this late phase of inflammation but the mechanisms for these actions of cAMP and of agents that elevate tissue cAMP levels are not well understood. In this article, we review the fibrotic process and focus on two recently recognized aspects of actions of cAMP and its effector Epac (Exchange protein activated by cAMP): a) blunting of epithelial‐mesenchymal transformation (EMT) and b) down‐regulation of Epac expression by pro‐fibrotic agents (e.g., TGF‐β, angiotensin II), which may promote... British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5582025 Tue, 10 Jan 2012 05:00:00 +0100 5582025 http://www.medworm.com/index.php?rid=5582024&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01848.x Conclusions and implications  These data support the hypothesis that CGRP stimulates angiogenesis in vivo directly by activating CGRP receptors. Capsaicin‐induced endothelial cell proliferation was completely blocked by co‐administration of CGRP and NK1 receptor antagonists, indicating that both CGRP and substance P may contribute to angiogenesis in this model of synovitis. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5582024 Tue, 10 Jan 2012 05:00:00 +0100 5582024 http://www.medworm.com/index.php?rid=5582023&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01849.x Conclusions and implications  Crizotinib reversed ABCB1‐mediated MDR by inhibiting ABCB1 transport function without involvement of ABCB1 expression or blockade of the Akt or Erk1/2 pathways. These findings are useful for combination chemotherapy of crizotinib with conventional chemotherapeutic drugs. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5582023 Tue, 10 Jan 2012 05:00:00 +0100 5582023 http://www.medworm.com/index.php?rid=5582022&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01850.x Conclusions and implications  These experiments suggest that escitalopram enhances, although moderately, cortical [NE]extin vivo by a direct mechanism involving the inhibition of the high‐affinity NE transporter (NET). (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5582022 Tue, 10 Jan 2012 05:00:00 +0100 5582022 http://www.medworm.com/index.php?rid=5582021&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01851.x SUMMARYThe Transient Receptor Potential Vanilloid 1 and Ankyrin 1 (TRPV1 and TRPA1, respectively) channels are members of the TRP superfamily of structurally related, non‐selective cation channels. It is rapidly becoming clear that the functions of TRPV1 and TRPA1 interlink with each other to a considerable extent. This is especially clear in relation to pain and neurogenic inflammation where TRPV1 is co‐expressed on the vast majority of TRPA1‐expressing sensory nerves and both integrate a variety of noxious stimuli. The more recent discovery that both TRPV1 and TRPA1 are expressed on a multitude of non‐neuronal sites has led to a plethora of research into possible functions of these receptors. Non‐neuronal cells on which TRPV1 and TRPA1 are expressed vary from vascular smooth mu... British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5582021 Tue, 10 Jan 2012 05:00:00 +0100 5582021 http://www.medworm.com/index.php?rid=5582020&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01852.x CONCLUSION AND IMPLICATIONS  This study provides the first evidence that the anti‐tumor effects of ES on glioblastoma cells is through direct inhibition of T‐type Ca2+ channels, and gives new insights into the future development of a new class of proliferation‐ and migration‐targeted anti‐glioblastoma agents. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5582020 Tue, 10 Jan 2012 05:00:00 +0100 5582020 http://www.medworm.com/index.php?rid=5582030&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01834.x Conclusions and Implications.  These data indicate RCS quenching with a D‐CAR ester is highly effective in attenuating experimental atherosclerosis and renal disease by reducing carbonyl stress and inflammation and that this may represent a promising therapeutic strategy in humans. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5582030 Mon, 09 Jan 2012 05:00:00 +0100 5582030 http://www.medworm.com/index.php?rid=5582029&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01835.x CONCLUSIONS AND IMPLICATIONS  Ascorbic acid, known to inhibit Cav3.2, functions to suppress the neuropathic hyperalgesia. DI‐VCP ointment for topical application is considered to help in treatment of neuropathic pain. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5582029 Mon, 09 Jan 2012 05:00:00 +0100 5582029 http://www.medworm.com/index.php?rid=5582028&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01836.x Conclusions and implications:  This multiparametric approach can reveal specific drug properties and provide translational information. Whereas the complex profile for p38 inhibition in AIA is not observed in human RA, immunosuppressants such as DHODH and JAK inhibitors show DMARD properties and side effects similar in both AIA and RA. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5582028 Mon, 09 Jan 2012 05:00:00 +0100 5582028 http://www.medworm.com/index.php?rid=5582027&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01837.x CONCLUSION AND IMPLICATIONS  μ‐CnIIIC potently blocks VGSCs in skeletal muscle and nerve, and hence is applicable to myorelaxation. Its new atypical pharmacological profile suggests some common structural features between VGSCs and nAChR channels. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5582027 Mon, 09 Jan 2012 05:00:00 +0100 5582027 http://www.medworm.com/index.php?rid=5572283&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01822.x SummaryBlood doping practices in sport have been around for at least half a century and will likely remain for several years to come. The main reason for the various forms of blood doping to be common is that they are easy to perform, and the effects on exercise performance are gigantic. Yet another reason for blood doping to be a popular illicit practice is that detection is difficult. For autologous blood transfusions for example, no direct test exists, and the direct testing of misuse with recombinant human erythropoietin has proven very difficult despite a test exists. Future blood doping practice will likely include the stabilization of the transcription factor Hypoxia Inducible Factor which leads to an increased endogenous erythropoietin synthesis. It seems unrealistic to develop spe... British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5572283 Fri, 06 Jan 2012 05:00:00 +0100 5572283 http://www.medworm.com/index.php?rid=5572282&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01823.x Conclusions and implications  T1AM (1.3 μg kg‐1) induces central and peripheral effects including hyperglycemia and reduction of plasma fT3 plasma in fasted mice. These effects critically depend on the concentration of T1AM or of some of its metabolites in target organs. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5572282 Fri, 06 Jan 2012 05:00:00 +0100 5572282 http://www.medworm.com/index.php?rid=5572281&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01831.x Conclusions and implications:  These results demonstrate that ATP activates P2X4/7 and P2Y2 receptors and up‐regulates proliferation by promoting cell cycling progression and also increases cell migration in cultured human cardiac fibroblasts, which may be involved in cardiac remodeling of injured hearts. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5572281 Fri, 06 Jan 2012 05:00:00 +0100 5572281 http://www.medworm.com/index.php?rid=5572280&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01832.x Conclusions and implications:  Taken together, these results suggest that the BP modulation effect of renin in the NTS involved AT1R and Mas receptor activations of Gq and Ras to evoke subsequent PI3K‐Akt‐eNOS signaling. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5572280 Fri, 06 Jan 2012 05:00:00 +0100 5572280 http://www.medworm.com/index.php?rid=5572290&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01824.x Conclusions and implications:  These data show that TZD‐induced SK‐1 up‐regulation results in lower amounts of CTGF, demonstrating novel facets for the anti‐fibrotic effects of this class of drugs (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5572290 Thu, 05 Jan 2012 05:00:00 +0100 5572290 http://www.medworm.com/index.php?rid=5572289&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01825.x Conclusions and implications:  Pioglitazone treatment, although did not reduce blood pressure in SHR, increased COX‐2‐derived PGI2 production, reduced oxidative stress, and increased NO bioavailability, all of them involved on vasoconstrictor responses in resistance arteries. These effects would contribute to the cardioprotective effect of glitazones reported in several pathologies. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5572289 Thu, 05 Jan 2012 05:00:00 +0100 5572289 http://www.medworm.com/index.php?rid=5572288&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01826.x SummaryControl of gene transcription is a major regulatory determinant for function of the endothelin pathway. Epigenetic mechanisms act on tissue‐specific gene expression during development and in response to physiological stimuli. Most of the limited evidence available on epigenetic regulation of the endothelin pathway focuses on the EDN1 and EDNRB genes. Examination of whole genome databases suggests that both genes are influenced by histone modifications and DNA methylation. This interpretation is supported by studies directed at detecting epigenetic action on the two genes. The clearest illustration of epigenetic factors altering endothelin signaling is DNA methylation‐associated EDNRB silencing during tumorigenesis. This review summarizes on our current understanding of epigeneti... British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5572288 Thu, 05 Jan 2012 05:00:00 +0100 5572288 http://www.medworm.com/index.php?rid=5572287&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01827.x SummaryThe cardiac hormone atrial natriuretic peptide (ANP) is critically involved in the maintenance of arterial blood pressure and intravascular volume homeostasis. Its cGMP‐producing guanylyl cyclase‐A (GC‐A) receptor is densely expressed in the microvascular endothelium of the lung and systemic circulation, but the functional relevance is controversial. Some studies reported that ANP stimulates endothelial cell permeability, whereas others described that the peptide attenuates endothelial barrier dysfunction provoked by inflammatory agents such as thrombin or histamine. Many studies in vitro addressed the effects of ANP on endothelial proliferation and migration. Again, both pro‐ and anti‐angiogenic properties were described. To unravel the role of the endothelial actions of ... British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5572287 Thu, 05 Jan 2012 05:00:00 +0100 5572287 http://www.medworm.com/index.php?rid=5572286&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01828.x In conclusion, such autoantibodies seem to cause or promote chronic human left ventricular dysfunction by acting on their receptor targets in a drug‐like fashion. However, the pharmacology of this interaction is poorly understood. It is unclear how the autoantibodies trigger changes in receptor activity and second messenger coupling and how that is related to the pathogenesis and severity of the associated diseases. Here, we summarise the available evidence regarding these issues and discuss these findings in the light of recent knowledge about the conformational activation of the human β2‐adrenergic receptor and the properties of bona fide cardio‐pathogenic autoantibodies derived from immune‐adsorption therapy of DCM patients. These considerations might contribute to the concepti... British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5572286 Thu, 05 Jan 2012 05:00:00 +0100 5572286 http://www.medworm.com/index.php?rid=5572285&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01829.x Conclusions and implications:  Triptolide enhances SMN protein production by promoting SMN2 activation, exon 7 inclusion and increasing nuclear gems, and extends survival in SMA mice, which suggests triptolide might be a potential target for SMA therapy. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5572285 Thu, 05 Jan 2012 05:00:00 +0100 5572285 http://www.medworm.com/index.php?rid=5572284&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01830.x Conclusions and implications:  These results demonstrate that inflammatory muscle pain involves a cascade of events that is dependent on the activation of PKC, p38 and JNK, and the synthesis of new IL‐1β, TNF‐α and IL‐6 associated with the up‐regulation of both B1 and B2 kinin receptors. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5572284 Thu, 05 Jan 2012 05:00:00 +0100 5572284 http://www.medworm.com/index.php?rid=5572279&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2012.01833.x Conclusions and implications:  CAPE is a novel type of neuroprotective agent whose actions are mediated by both HO‐1 and BDNF. These findings may provide a novel clue to develop neuroprotective pharmaceuticals for treatment of neurodegenerative disorders. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5572279 Sun, 01 Jan 2012 05:00:00 +0100 5572279 http://www.medworm.com/index.php?rid=5524947&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01821.x Conclusions and implications:  These results indicate that flupirtine exerts its analgesic action by acting on both, GABAA receptors and Kv7 channels. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5524947 Thu, 22 Dec 2011 06:45:10 +0100 5524947 http://www.medworm.com/index.php?rid=5524953&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01817.x Conclusions and implications.  PGE2 stimulation of the human EP1 receptor upregulates the expression of Nurr1 by a mechanism involving the sequential activation of the Rho, PKA, CREB and NF‐κB signaling pathways. EP1 receptors are implicated with tumorigenesis and the upregulation of Nurr1 may underlie the anti‐apoptotic effects of PGE2. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5524953 Tue, 20 Dec 2011 05:00:00 +0100 5524953 http://www.medworm.com/index.php?rid=5524951&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01816.x Conclusion and Implications:  We conclude that steroid accumulation in plasma membrane is the route by which it accesses a binding site on the NMDAR. Thus, our results provide a possible structural framework for pharmacologically targeting the transmembrane domains of the receptor. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5524951 Tue, 20 Dec 2011 05:00:00 +0100 5524951 http://www.medworm.com/index.php?rid=5524950&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01818.x SummaryRepolarization dependent cardiac arrhythmias only arise in hearts facing multiple ‘challenges’ affecting its so‐called repolarization reserve. Congestive heart failure (CHF) is one such challenge frequently observed in humans and is accompanied by altered calcium handling within the contractile heart cell. This raises the question as to whether or not the well known calcium antagonist verapamil acts as an antiarrhythmic in this setting, as seen in arrhythmia models without CHF. According to the study of Milberg et al. in this issue of BJP the answer is yes. The results of this study, using a rabbit CHF model, raise important questions. First, given that the model combines CHF with a number of other interventions that predispose towards arrhythmia, will similar conclusions be r... British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5524950 Tue, 20 Dec 2011 05:00:00 +0100 5524950 http://www.medworm.com/index.php?rid=5524949&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01819.x Abstract3,4‐Methyleneddioxymethamphatamine (MDMA) induces both acute adverse effects and long‐term neurotoxic loss of brain 5‐HT neurones in laboratory animals. However, when choosing doses, most preclinical studies have paid little attention to the pharmacokinetics of the drug in humans or animals. The recreational use of MDMA and current clinical investigations of the drug for therapeutic purposes demand better translational pharmacology to allow accurate risk assessment of its ability to induce adverse events. Recent pharmacokinetic studies on MDMA in animals and humans are reviewed and indicate that the risks following MDMA ingestion should be re‐evaluated. Acute behavioural and body temperature changes result from rapid MDMA‐induced monoamine release, while long‐term neuro... British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5524949 Tue, 20 Dec 2011 05:00:00 +0100 5524949 http://www.medworm.com/index.php?rid=5524948&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01820.x CONCLUSIONS AND IMPLICATIONS  SP in the LC exerted analgesic effects on neuropathic pain through NK1 receptor activation and resulted in facilitation of spinal noradrenergic transmission. Accordingly, manipulation of the SP/NK1 receptor signalling pathway in the LC may be a promising strategy for effective medication for neuropathic pain. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5524948 Tue, 20 Dec 2011 05:00:00 +0100 5524948 http://www.medworm.com/index.php?rid=5515587&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01806.x (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5515587 Mon, 19 Dec 2011 06:39:19 +0100 5515587 http://www.medworm.com/index.php?rid=5515586&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01592.x CONCLUSIONS AND IMPLICATIONS Our results show that bisphosphonate exposure leads to impaired neutrophil chemotaxis, neutrophil NADPH oxidase activity and reduced circulating neutrophil counts. This work suggests that bisphosphonates have the potential to depress the innate immune system for a prolonged time, possibly contributing to the pathogenesis of BRONJ. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5515586 Mon, 19 Dec 2011 06:39:17 +0100 5515586 http://www.medworm.com/index.php?rid=5515585&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01584.x CONCLUSIONS AND IMPLICATIONS Our data indicate that the oxidative species ONOO‐ and H2O2 increase arginase activity/expression through PKC‐mediated activation of RhoA/Rho kinase pathway. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5515585 Mon, 19 Dec 2011 06:39:14 +0100 5515585 http://www.medworm.com/index.php?rid=5515584&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01575.x CONCLUSION AND IMPLICATIONS The novel neurotrophic and neuroprotective effects of SAHA demonstrated in this study suggest that further study of this HDAC inhibitor could provide a new therapeutic approach to the treatment of neurodegenerative diseases. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5515584 Mon, 19 Dec 2011 06:39:13 +0100 5515584 http://www.medworm.com/index.php?rid=5515583&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01581.x CONCLUSION AND IMPLICATIONS These results indicate that negative regulation of Akt signalling and MMP‐2 by rVP1 may have the potential to suppress ovarian tumour growth and metastasis in vivo. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5515583 Mon, 19 Dec 2011 06:39:11 +0100 5515583 http://www.medworm.com/index.php?rid=5515582&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01558.x CONCLUSION AND IMPLICATIONSIsolated cardiomyocytes lack specificity to discriminate between TdP liability of the IKr blocking drugs moxifloxacin and dofetilide or E4031. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5515582 Mon, 19 Dec 2011 06:39:10 +0100 5515582 http://www.medworm.com/index.php?rid=5515581&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01563.x CONCLUSION AND IMPLICATIONS The NPFF system is involved in the development of two major undesirable effects: tolerance and dependence, which are clinically associated with prolonged exposure to opiates. Our findings suggest that NPFF receptors are interesting therapeutic targets to improve the analgesic efficacy of opiates by limiting the development of tolerance, and for the treatment of opioid dependence. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5515581 Mon, 19 Dec 2011 06:39:05 +0100 5515581 http://www.medworm.com/index.php?rid=5515580&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01561.x CONCLUSIONS AND IMPLICATIONS GPBA signalling in L‐cells involves rapid elevation of cAMP, and enhanced calcium and secretory responses to glucose. Modulation of this receptor therapeutically may be an attractive strategy to enhance GLP‐1 secretion and achieve better glycaemic control in diabetic patients. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5515580 Mon, 19 Dec 2011 06:39:03 +0100 5515580 http://www.medworm.com/index.php?rid=5515579&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01534.x CONCLUSIONS AND IMPLICATIONS These data indicate that a cluster of positively charged residues at the base of the cysteine‐rich head region can account for the highly selective antagonism of the P2X1 receptor by the suramin derivative NF449. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5515579 Mon, 19 Dec 2011 06:39:00 +0100 5515579 http://www.medworm.com/index.php?rid=5515578&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01570.x The p53 tumour suppressor blocks cancer development by triggering apoptosis or cellular senescence in response to oncogenic stress or DNA damage. Consequently, the p53 signalling pathway is virtually always inactivated in human cancer cells. This unifying feature has commenced tremendous efforts to develop p53‐based anti‐cancer therapies. Different strategies exist that are adapted to the mechanisms of p53 inactivation. In p53‐mutated tumours, delivery of wild‐type p53 by adenovirus‐based gene therapy is now practised in China. Also, remarkable progress has been made in the development of p53‐binding drugs that can rescue and reactivate the function of mutant or misfolded p53. Other biologic approaches include the development of oncolytic viruses that are designed to specifical... British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5515578 Mon, 19 Dec 2011 06:38:51 +0100 5515578 http://www.medworm.com/index.php?rid=5515577&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01557.x The drug efflux pump P‐glycoprotein (P‐gp) plays an important role in the function of the blood–brain barrier by selectively extruding certain endogenous and exogenous molecules, thus limiting the ability of its substrates to reach the brain. Emerging evidence suggests that P‐gp may restrict the uptake of several antidepressants into the brain, thus contributing to the poor success rate of current antidepressant therapies. Despite some inconsistency in the literature, clinical investigations of potential associations between functional single nucleotide polymorphisms in ABCB1, the gene which encodes P‐gp, and antidepressant response have highlighted a potential link between P‐gp function and treatment‐resistant depression (TRD). Therefore, co‐administration of P‐gp inhibi... British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5515577 Mon, 19 Dec 2011 06:38:48 +0100 5515577 http://www.medworm.com/index.php?rid=5505055&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01815.x CONCLUSION AND IMPLICATIONS  These results suggest that dopamine at lower concentrations preferentially inhibits sVRP, which is mediated via D1‐like and unidentified receptors. The dopamine‐evoked depression is involved in modulating the spinal functions by the descending dopaminergic pathways. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5505055 Fri, 16 Dec 2011 06:43:54 +0100 5505055 http://www.medworm.com/index.php?rid=5505059&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01811.x Discussions” and United States (US) Food and Drug Administration (FDA) “Pharmacology/Toxicology Reviews” and package inserts (USPI). Data on the 15 approved biopharmaceuticals were included: abatacept; abciximab; alefacept; alemtuzumab; basiliximab; cetuximab; daclizumab; efalizumab; ipilimumab; muromonab; natalizumab; panitumumab; rituximab; tocilizumab and trastuzumab. For statistical analysis of concordance, data from these 15 were combined with data on the approved mAbs and fusion proteins directed toward soluble targets. Good concordance with human pharmacodynamics was found for mice receiving surrogates or non human primates (NHP) receiving the human pharmaceutical. In contrast, there was poor concordance for human pharmacodynamics in genetically deficient mice and for human ad... British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5505059 Tue, 13 Dec 2011 05:00:00 +0100 5505059 http://www.medworm.com/index.php?rid=5505058&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01812.x Discussions” and United States Food and Drug Administration (FDA) “Pharmacology/Toxicology Reviews” and package inserts (USPIs). Data on the following approved biopharmaceuticals were included: adalimumab; anakinra; bevacizumab;; canakinumab; certolizumab pegol; denosumab; eculizumab; etanercept; golimumab; infliximab; omalizumab; ranibizumab; rilonacept and ustekinumab. Some related biopharmaceuticals in late stage development were also included for comparison. Good concordance with human pharmacodynamics was found for both non‐human primates receiving the human biopharmaceutical and mice receiving rodent homologues (surrogates). In contrast, there was limited concordance for human adverse effects in genetically deficient mice, mice receiving surrogates or Non‐Human Primates (NH... British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5505058 Tue, 13 Dec 2011 05:00:00 +0100 5505058 http://www.medworm.com/index.php?rid=5505057&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01813.x Conclusions and implications.  In summary, we report PKC‐dependent modulation of K2P18.1 background currents. Activation of K2P18.1 through protein kinase C may serve as novel molecular target for migraine treatment. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5505057 Tue, 13 Dec 2011 05:00:00 +0100 5505057 http://www.medworm.com/index.php?rid=5505056&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01814.x Conclusions and implications:  Individual cells are well‐coupled to each other within EC tubes. Inhibiting GJCs with glycyrrhetinic acid derivatives coincides with loss of hyperpolarization mediated by IKCa/SKCa irrespective of Ca2+ signaling, obviating use of these agents in resolving key determinants of electrical conduction along the endothelium. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5505056 Tue, 13 Dec 2011 05:00:00 +0100 5505056 http://www.medworm.com/index.php?rid=5476726&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01559.x CONCLUSION AND IMPLICATIONS Okadaic acid induced MMP‐9 activity through p38 MAPK and was inhibited by isoprenaline via a pathway involving β‐arrestin 2, PP2A and an NF‐κB binding motif. These findings elucidate how phosphoprotein phosphatases and adrenoceptors may modulate tissue remodelling by affecting fibroblast function. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5476726 Wed, 07 Dec 2011 06:58:15 +0100 5476726 http://www.medworm.com/index.php?rid=5476725&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01545.x CONCLUSIONS AND IMPLICATIONS We propose that these compounds have novel properties including inhibition of bFGF‐mediated endothelial responses and perturbation of VEGFR2 trafficking. Differential inhibitor binding to receptor tyrosine kinases translates into more potent inhibition of bFGF‐ and VEGF‐A‐mediated intracellular signalling, cell migration and tubulogenesis. Indolinones and anilinophthalazines thus belong to a class of multi‐kinase inhibitors that show clinical efficacy in disease therapy. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5476725 Wed, 07 Dec 2011 06:58:12 +0100 5476725 http://www.medworm.com/index.php?rid=5476724&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01553.x CONCLUSIONS AND IMPLICATIONS The expression of major NMDA receptor subtypes, GluN1, GluN2A and GluN2B in the chick retina makes them pertinent targets for pharmacological inhibition of SD. The high efficacy of NVP‐AAM077 on SD inhibition suggests a critical role of GluN2A‐containing receptors in SD genesis. Such high anti‐SD potency suggests that NVP‐AAM077, and other GluN2A‐selective drug‐like candidates, could be potential anti‐migraine agents. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5476724 Wed, 07 Dec 2011 06:58:11 +0100 5476724 http://www.medworm.com/index.php?rid=5476723&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01546.x CONCLUSIONS AND IMPLICATIONS Activation of endothelial KCa3.1 and KCa2.3 lowers arterial blood pressure in dogs by an immediate electrical vasodilator mechanism. The results support the concept that pharmacological activation of these channels may represent a potential unique endothelium‐specific antihypertensive therapy. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5476723 Wed, 07 Dec 2011 06:58:09 +0100 5476723 http://www.medworm.com/index.php?rid=5476722&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01540.x CONCLUSION AND IMPLICATIONS Intermedin stabilized endothelial barriers in HUVEC monolayers via CLR/RAMP2 receptors. These effects were mediated via cAMP‐mediated inactivation of contractility and strengthening of cell–cell adhesion. These findings identify intermedin as a barrier stabilizing agent and suggest intermedin as a potential treatment for vascular leakage in inflammatory conditions. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5476722 Wed, 07 Dec 2011 06:58:08 +0100 5476722 http://www.medworm.com/index.php?rid=5476721&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01535.x CONCLUSIONS AND IMPLICATIONS P2X7 receptors were significantly involved in a model of HC induced by cyclophosphamide. Pharmacological inhibition of these receptors might represent a new therapeutic option for this pathological condition. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5476721 Wed, 07 Dec 2011 06:58:05 +0100 5476721 http://www.medworm.com/index.php?rid=5476720&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01526.x CONCLUSIONS AND IMPLICATIONS This is the first study to show that Bp44mT can be given orally with potent anti‐tumour efficacy. Oral administration of a novel and effective chemotherapeutic agent provides the benefits of convenience for chronic dosing regimens. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5476720 Wed, 07 Dec 2011 06:58:02 +0100 5476720 http://www.medworm.com/index.php?rid=5476719&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01521.x CONCLUSIONS AND IMPLICATIONS Knockdown of AE1 expression in gastric mucosa by administration of synthetic siRNAs significantly inhibits the growth of gastric cancer and decreases the detection rate of this tumour in experimental mice. These results suggest that AE1 is potentially a key therapeutic target and the silencing of AE1 expression in gastric mucosa could provide a new therapeutic approach for treating gastric cancer. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5476719 Wed, 07 Dec 2011 06:58:00 +0100 5476719 http://www.medworm.com/index.php?rid=5476718&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01485.x CONCLUSIONS AND IMPLICATIONS Increased vascular reactivity to agonists in SAH was attributable to the enhancement and prolongation of the contractile response. A combination of argatroban and anti‐oxidative agents was required to prevent both the enhancement and prolongation of the contractile response.LINKED ARTICLE This article is commented on by Hollenberg, pp. 103–105 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476‐5381.2011.01564.x (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5476718 Wed, 07 Dec 2011 06:57:58 +0100 5476718 http://www.medworm.com/index.php?rid=5476717&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01533.x α2‐Adrenoceptors are important mediators of physiological responses to the endogenous catecholamines noradrenaline and adrenaline. In addition, α2‐adrenoceptors are pharmacological targets for the treatment of hypertension, sympathetic overactivity and glaucoma. α2‐Adrenoceptors are also targeted to induce sedation and analgesia in anaesthesia and intensive care. α2‐Adrenoceptors were first described as presynaptic receptors inhibiting the release of various transmitters from neurons in the central and peripheral nervous systems. In addition to these presynaptic neuronal receptors, α2‐adrenoceptors were also identified in many non‐neuronal cell types of the body. Gene‐targeting in mice provided a comprehensive assignment of the physiological and pharmacological functions... British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5476717 Wed, 07 Dec 2011 06:57:54 +0100 5476717 http://www.medworm.com/index.php?rid=5476716&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01538.x The ancestral status of oestrogen receptor (ER) in the family of the steroid receptors has probably contributed to the pleiotropic actions of oestrogens, and in particular, that of 17β‐oestradiol (E2). Indeed, in addition to their well‐described role in sexual development and reproduction, they influence most of the physiological processes. The pathophysiological counterpart of these actions includes prevention of osteoporosis, atheroma and type 2 diabetes, and also the promotion of uterus and breast cancer growth. Thus, the major challenge consists in uncoupling some beneficial actions from other deleterious ones, that is, selective ER modulation. Tamoxifen and raloxifene are already used, as they prevent the recurrence of breast cancer and mimic oestrogen action mainly on bone. Both... British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5476716 Wed, 07 Dec 2011 06:57:49 +0100 5476716 http://www.medworm.com/index.php?rid=5476706&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01808.x SummaryLife‐threatening diseases of the cardiovascular system, like atherosclerosis, are exacerbated by unwanted inflammation within the structures of large blood vessels. This inflammation involves increased permeability of the vascular endothelial cells (VECs) that form the lining of blood vessels, leading to exaggerated extravasation of blood components and accumulation of fluid in the extravascular space. This results in tissue dysfunction and increased secretion of chemokines that attract leukocytes and monocytes to the inflamed endothelium. Cyclic AMP is synthesised in VECs in response to endogenous Gs‐coupled receptors and is known to limit cytokine action and reduce endothelial hyperpermeability induced by multiple pro‐inflammatory stimuli. The mechanisms underlying this anti... British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5476706 Wed, 07 Dec 2011 06:51:17 +0100 5476706 http://www.medworm.com/index.php?rid=5476707&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01807.x Conclusions and Implications.  These studies reveal OGR1 to be a physiologically‐relevant GPCR in ASM cells, capable of pleiotropic signaling and mediation of contraction in response to small reductions in extracellular pH. Accordingly, ASM OGR1 may contribute to asthma pathology and represent a therapeutic target in obstructive lung diseases. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5476707 Tue, 06 Dec 2011 05:00:00 +0100 5476707 http://www.medworm.com/index.php?rid=5476715&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01798.x SummaryHyperpolarization‐activated cation channels generate the If current in the heart. In the sinoatrial node, If is thought to play an essential role in setting the heart rate and mediating its autonomic control. This review focuses on the role of If in pacemaking and non‐pacemaking cardiomyocytes and the resulting therapeutic implications. HCN4 represents the principal isoform underlying sinoatrial If, but other isoforms may also be of importance. To examine the functional role of cardiac channels, several mouse mutants, most of them targeting HCN4, have been generated by different groups. Unexpectedly, these lines display greatly different and as yet unexplained phenotypes. We provide an overview about these HCN mutants and suggest an interpretation of the functional significance ... British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5476715 Mon, 05 Dec 2011 05:00:00 +0100 5476715 http://www.medworm.com/index.php?rid=5476714&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01799.x Conclusions and implications:  Our results establish that liposomes are suitable nanocarriers for the delivery of P‐I, and that the antitumor potential of liposomal P‐I merits further evaluation. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5476714 Mon, 05 Dec 2011 05:00:00 +0100 5476714 http://www.medworm.com/index.php?rid=5476713&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01800.x SummaryCyclic AMP is the intracellular second messenger for a variety of immunoregulatory inflammatory mediators such as prostaglandin E2, adenosine and histamine that signal to effector T cells from monocytes, macrophages and regulatory T cells. Protein kinase A type I localizes to lipid rafts in effector T cells during T cell activation and directly modulates proximal signal events including phosphorylation of Csk, which initiates a negative signal pathway that fine‐tunes the T cell activation process. The PKA‐Csk immunoregulatory pathway is scaffolded by the A kinase anchoring protein Ezrin, the Csk binding protein PAG and the linker protein EBP50. This pathway is hyperactivated in chronic infections with an inflammatory component such as HIV, other immune deficiencies and around so... British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5476713 Mon, 05 Dec 2011 05:00:00 +0100 5476713 http://www.medworm.com/index.php?rid=5476712&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01801.x Conclusions and implications:  This is the first report that describes an anti‐angiogenic inhibitor based on such a pyrazole core. Using a de novo structure‐based identification approach is an attractive method to aid such drug discovery. The reported efficacy and selectivity of JK‐P3 provides sufficient scope for further drug development. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5476712 Mon, 05 Dec 2011 05:00:00 +0100 5476712 http://www.medworm.com/index.php?rid=5476711&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01803.x Conclusions and Implications:  The human CLR ECL3 is crucial for AM‐induced cAMP responses via three CLR/RAMP heterodimers, and activation of these heterodimers probably relies on AM‐induced conformational changes. This study provides a clue to the molecular basis of the activation of RAMP‐based Family B GPCRs. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5476711 Mon, 05 Dec 2011 05:00:00 +0100 5476711 http://www.medworm.com/index.php?rid=5476710&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01802.x Conclusions and implications:  17β‐Estradiol prevents the doxorubicin‐induced cell shrinkage mediated through activation of ICl,vol and subsequent induction of apoptosis signals, thorough a membrane receptor‐dependent PI3K pathway in rabbit articular chondrocytes. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5476710 Mon, 05 Dec 2011 05:00:00 +0100 5476710 http://www.medworm.com/index.php?rid=5476709&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01804.x Conclusions and implications:  Our study suggested that ethyl pyruvate improved the glial microenvironment and promoted axon regeneration and functional recovery, shedding light on the potential therapeutic benefit for SCI. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5476709 Mon, 05 Dec 2011 05:00:00 +0100 5476709 http://www.medworm.com/index.php?rid=5476708&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01805.x Conclusions and Implications:  Synapse loss may be a mechanism to protect from excess excitatory input. Thus, memantine and ifenprodil are promising neuroprotective drugs because they spare synaptic changes and promote survival. These NR2B‐prefering drugs induced recovery from Tat‐evoked synapse loss, suggesting that synaptic pharmacology changed during the neurotoxic process. NMDA receptor subtypes differentially participate in the adaptation and death induced by excitotoxic insult. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5476708 Mon, 05 Dec 2011 05:00:00 +0100 5476708 http://www.medworm.com/index.php?rid=5457907&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01797.x AbstractBackground and purpose  Amphibian Bv8 injected in rodents induces potent nociceptive sensitisation. Its mammalian homologue, PROK2, is strongly up‐regulated in inflamed tissues and is a major determinant in triggering inflammatory pain. Bv8 and PROK2 activate two closely related GPCRs, PK1 and PK2, in a relatively non‐selective fashion. To characterize better the two receptors′ roles in hyperalgesia and to obtain ligands whose binding affinity and efficacy differed for the two receptors we modified the Bv8 sequence in regions essential for receptor recognition and activation.Experimental approach  We tested the Bv8 analogue modified by substituting Trp with Ala in position 24 (A‐24) and compared it with Bv8 for its ability to bind to and activate PK1 and PK2 in cell pre... British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5457907 Thu, 01 Dec 2011 05:00:00 +0100 5457907 http://www.medworm.com/index.php?rid=5457914&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01790.x Conclusions and implications  The biological and metabolic profiles of these TLR7‐selective antedrug compounds are consistent with a new class of compound that could be administrated locally for the treatment of allergic diseases whilst reducing the risk of systemic side effects. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5457914 Tue, 29 Nov 2011 05:00:00 +0100 5457914 http://www.medworm.com/index.php?rid=5457913&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01791.x Conclusions and Implications:  In the experimental models studied, the β‐adrenergic agonists inhibit breast cancer cell proliferation and tumour growth. This effect is probably mediated by Erk 1/2 phosphorylation inhibition. The β‐adrenergic agonists perform equally well as the α2‐adrenergic antagonist rauwolscine, providing possible novel therapeutic adjuvant treatments for breast cancer. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5457913 Tue, 29 Nov 2011 05:00:00 +0100 5457913 http://www.medworm.com/index.php?rid=5457912&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01792.x AbstractMetastatic bone disease is a serious clinical complication for the treatment of patients with advanced cancer, yet few therapeutic options are currently available. Bisphosphonates are an established standard‐of‐care for these patients, but new treatments are now emerging, including the use of monoclonal antibodies targeting RANK ligand. In this issue of BJP, Reuter et al., provide evidence that thiocolchicoside, a semi‐synthetic derivative of the naturally occurring colchicoside, extracted from the seeds of Gloriosa superba (liliaceae), prevents osteoclactogenesis by suppressing RANK ligand‐mediated NF‐κB activation. Thiolcolchicoside may thus represent an attractive therapeutic option for the management of bone metastatic disease. (Source: British Journal of Pharmacolog... British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5457912 Tue, 29 Nov 2011 05:00:00 +0100 5457912 http://www.medworm.com/index.php?rid=5457911&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01793.x SummaryMutations, even if not directly in the ligand binding sites of proteins, can lead to disease. In cell surface receptors, this can happen if they uncouple conformational changes that take place upon agonist (or, antagonist) binding the extracellular domain and the intracellular response. Uncoupling can take place by disrupting a major allosteric propagation pathway between the extra‐ and intra‐cellular domains. Here, I provide a mechanistic explanation: I first describe how propagation takes place; second, what can happen in the presence of a disease‐related mutation which is away from the binding site; and finally, how drugs may overcome this disruption and rescue function. The glycine receptor (GlyR) α1 subunit α1R271Q/L mutations which cause the neuromotor disorder are suc... British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5457911 Tue, 29 Nov 2011 05:00:00 +0100 5457911 http://www.medworm.com/index.php?rid=5457910&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01794.x Conclusions and implications: Our results show that ST0702 is an effective inhibitor of TCIPA in vitro. The salicylate metabolite may contribute to the effects of ST0702 by inhibiting ADP‐mediated TCIPA. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5457910 Tue, 29 Nov 2011 05:00:00 +0100 5457910 http://www.medworm.com/index.php?rid=5457909&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01795.x Conclusions and implications:  A decreased E‐M window was consistently observed with drugs documented to have high TdP risk, but not with drugs with low or no TdP risk. These results suggest the E‐M window in anaesthetized guinea‐pigs is a risk marker for TdP in man. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5457909 Tue, 29 Nov 2011 05:00:00 +0100 5457909 http://www.medworm.com/index.php?rid=5457908&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01796.x Abstract/summaryA‐kinase anchoring proteins (AKAPs) crucially contribute to the spatial and temporal control of cellular signalling. They directly interact with a variety of protein binding partners and cellular constituents thereby directing pools of signalling components to defined locales. In particular, AKAPs mediate compartmentalisation of cAMP signalling. Alterations in AKAP expression and their interactions are associated with or cause diseases including chronic heart failure, various cancers and disorders of the immune system such as HIV. A number of cellular dysfunctions result from mutations of specific AKAPs. The link between malfunctions of single AKAP complexes and a disease makes AKAPs and their interactions interesting targets for the development of novel drugs. (Source: B... British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5457908 Tue, 29 Nov 2011 05:00:00 +0100 5457908 http://www.medworm.com/index.php?rid=5449863&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01787.x CONCLUSIONS AND IMPLICATIONS  Shortening of N‐terminus or mutation of glycosylation sites located within the N‐terminus enhanced receptor internalization but impaired the surface expression of D2R. N‐terminal region of D2R, in a sequence‐specific manner, controls receptor conformation and integration into the plasma membrane, which determine the subcellular localization, intracellular trafficking and signaling properties of D2R. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5449863 Mon, 28 Nov 2011 06:49:55 +0100 5449863 http://www.medworm.com/index.php?rid=5449864&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01786.x SummaryEndothelin‐2 (ET‐2, also known as vasoactive intestinal contractor or VIC, in rodents) differs from endothelin‐1 (ET‐1) by only two amino acids, and unlike the third isoform, endothelin‐3 (ET‐3), it has the same affinity as ET‐1 for both ETA and ETB receptors. It is often assumed that ET‐2 would mimic the actions of the more abundant ET‐1 and current pharmacological interventions used to inhibit the ET system would also block the actions of ET‐2. These assumptions have focused research on ET‐1 with ET‐2 studied in much less detail. Recent research suggests that our understanding of the ET family requires re‐evaluation. Although ET‐2 is very similar in structure as well as pharmacology to ET‐1, and may co‐exist in the same tissue compartments, there is... British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5449864 Fri, 25 Nov 2011 05:00:00 +0100 5449864 http://www.medworm.com/index.php?rid=5431874&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01539.x CONCLUSIONS AND IMPLICATIONS These results indicate that the vascular KATP channel is one of the targets of rosiglitazone action, through which this drug may compromise coronary responses to circulating vasodilators and perhaps also to metabolic stress. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5431874 Tue, 22 Nov 2011 06:47:43 +0100 5431874 http://www.medworm.com/index.php?rid=5431873&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01518.x CONCLUSIONS AND IMPLICATIONS Our data suggested that Sal B effectively suppressed maturation of h‐monDC induced by ox‐LDL through PPARγ activation. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5431873 Tue, 22 Nov 2011 06:47:39 +0100 5431873 http://www.medworm.com/index.php?rid=5431872&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01517.x CONCLUSIONS AND IMPLICATIONS Sildenafil improved cognitive functions in Tg2576 mice and the effect was not related to changes in the amyloid burden. These data further strengthen the potential of sildenafil as a therapeutic agent for Alzheimer's disease. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5431872 Tue, 22 Nov 2011 06:47:38 +0100 5431872 http://www.medworm.com/index.php?rid=5431871&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01508.x CONCLUSIONS AND IMPLICATIONS Activation of TrkB, followed by recruitment of Shc/Grb2/SOS adaptor proteins, leading to activation of Ras/Raf‐1/ERK signalling pathway plays a crucial role in ameliorating central cardiovascular regulatory dysfunction via up‐regulation of NOS I/PKG signalling cascade in the RVLM in brain stem death. These findings provide novel information for developing therapeutic strategies against this fatal eventuality. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5431871 Tue, 22 Nov 2011 06:47:36 +0100 5431871 http://www.medworm.com/index.php?rid=5431870&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01523.x CONCLUSIONS AND IMPLICATIONS This pharmacological profile suggests that aldosterone, and possibly 10 µM spironolactone, use mechanisms that are dependent on PR and/or GR, but not MR, to inhibit iNOS induction in RASMC. With 50 µM spironolactone, other inhibitory mechanisms requiring further investigation may become predominant. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5431870 Tue, 22 Nov 2011 06:47:35 +0100 5431870 http://www.medworm.com/index.php?rid=5431869&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01496.x CONCLUSIONS AND IMPLICATIONS Both antibodies recognized NBCe1, but they had opposing effects on the function of this transporter, as the a‐L3 was inhibitory and the a‐L4 was excitatory. These antibodies could be valuable in studies on the pathophysiology of NBCe1 in cardiac tissue, opening a path for their potential clinical use. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5431869 Tue, 22 Nov 2011 06:47:31 +0100 5431869 http://www.medworm.com/index.php?rid=5431868&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01499.x CONCLUSIONS AND IMPLICATIONS The neurochemical and functional properties of mephedrone resemble those of MDMA, but it also shows an amphetamine‐like effect in that it evokes a rapid release and elimination of DA in the brain reward system, a feature that may contribute to its potent re‐inforcing properties. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5431868 Tue, 22 Nov 2011 06:47:28 +0100 5431868 http://www.medworm.com/index.php?rid=5431867&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01492.x CONCLUSION AND IMPLICATIONS Our results indicate that RBP4 is positively associated with markers of inflammation in obese and pro‐atherogenic conditions and could play a role in a predisposition to atherosclerosis. Furthermore, our results indicate that rimonabant may improve vascular function by modulating RBP4 along with pro‐inflammatory cytokines. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5431867 Tue, 22 Nov 2011 06:47:26 +0100 5431867 http://www.medworm.com/index.php?rid=5431866&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01481.x CONCLUSIONS AND IMPLICATIONS FXR was essential to maintain gastric and intestinal mucosal barriers. FXR agonists protected against gastric injury caused by ASA and NSAIDs by a CSE‐mediated mechanism. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5431866 Tue, 22 Nov 2011 06:47:25 +0100 5431866 http://www.medworm.com/index.php?rid=5431864&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01785.x Conclusions and implications:  β‐AR activates cAMP/Epac/PKCδ/p38 MAPK pathway to produce IL‐6 in NMCFs. This study identifies the missing link between cAMP and p38 MAPK signaling pathways and demonstrates that PKCδ can function as a novel downstream effector of β‐AR/cAMP/Epac pathway. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5431864 Tue, 22 Nov 2011 06:40:12 +0100 5431864 http://www.medworm.com/index.php?rid=5431865&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01784.x Conclusions and implications:  Dronedarone abolishes RAP‐induced ventricular microcirculatory abnormalities by reducing oxidative stress/ischemia related gene and protein expression in the ventricle. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5431865 Mon, 21 Nov 2011 05:00:00 +0100 5431865 http://www.medworm.com/index.php?rid=5422296&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01783.x CONCLUSIONS AND IMPLICATIONS  There is a direct relationship between the disassembly of the chaperone complex and the progression of neuronal differentiation upon stimulation with the immunophilin ligand FK506. Both neuronal differentiation and neuroregeneration appear to be mechanistically linked, so the elucidation of one mechanism may lead to unravel the properties of the other. The study also implies that the generation of FK506 derivatives devoid of immunosuppressive action would be therapeutically significant for neurotrophic use. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5422296 Sat, 19 Nov 2011 06:44:44 +0100 5422296 http://www.medworm.com/index.php?rid=5422298&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01781.x SummaryConotoxins (conopeptides) are small disulfide bonded peptides from the venom of marine cone snails. These peptides target a wide variety of membrane receptors, ion channels and transporters, and have enormous potential for a range of pharmaceutical applications. Structurally related ω‐conotoxins bind directly to and selectively inhibit neuronal (N)‐ type voltage‐gated calcium channels (VGCCs) of nociceptive primary afferent neurones. Among these, ω‐conotoxin MVIIA (Prialt) is approved by the FDA as an alternative intrathecal analgesic for the management of chronic intractable pain, particularly in patients refractory to opioids. A series of newly discovered ω‐conotoxins from Conus catus, including CVID−F, are potent and selective antagonists of N‐type VGCCs. In spin... British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5422298 Fri, 18 Nov 2011 05:00:00 +0100 5422298 http://www.medworm.com/index.php?rid=5422297&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01782.x Conclusions.  Our results identified novel and highly selective HCN isoform blockers, EC18 and MEL57A; the selectivity found in recombinant system was maintained in various tissues expressing different HCN isoforms. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5422297 Fri, 18 Nov 2011 05:00:00 +0100 5422297 http://www.medworm.com/index.php?rid=5408387&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01304.x : The following article from British Journal of Pharmacology, ‘Ion channel blocking profile of compounds with reported torsadogenic effects: What can be learned?’ by A. Ouillé, P. Champéroux, E. Martel, F. Ferro, D. Bouard, S. Richard, S. Richard and J.‐Y. Le Guennec (http://dx.doi.org/10.1111/j.1476‐5381.2011.01304.x), posted online on 8 March 2011 on Wiley Online Library (http://onlinelibrary.wiley.com), has been retracted by agreement between the journal Editor in Chief, Professor J.C. (Ian) McGrath and Blackwell Publishing Ltd. The retraction has been agreed due to duplication of research data from the following article in Journal of Pharmacological and Toxicological Methods, ‘A step towards characterisation of electrophysiological profile of torsadogenic drugs’ by Pascal... British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5408387 Wed, 16 Nov 2011 21:55:54 +0100 5408387 http://www.medworm.com/index.php?rid=5408386&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01477.x CONCLUSIONS AND IMPLICATIONS These results support the use of isoflavones in diet‐induced obesity, especially when hepatic steatosis is present and open a new field of use for these natural products. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5408386 Wed, 16 Nov 2011 21:55:52 +0100 5408386 http://www.medworm.com/index.php?rid=5408385&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01458.x CONCLUSIONS AND IMPLICATIONS RA‐V exhibited anti‐angiogenic activities in HUVEC and HMEC‐1 cell lines with changes in function of these endothelial cells. The underlying mechanisms of action involved the ERK1/2 signalling pathway. However, RA‐V may regulate different signalling pathways in different endothelial cells. These findings suggest that RA‐V has the potential to be further developed as an anti‐angiogenic agent. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5408385 Wed, 16 Nov 2011 21:55:51 +0100 5408385 http://www.medworm.com/index.php?rid=5408384&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01442.x CONCLUSIONS AND IMPLICATIONS At 4 h after DEP exposure, the cardiovascular changes did not appear to result from pulmonary inflammation but possibly from the entry of DEP and/or their associated components into blood. However, at 18 h, DEP induced significant changes in pulmonary and cardiovascular functions along with lung inflammation. Pretreatment with thymoquinone prevented DEP‐induced cardiovascular changes. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5408384 Wed, 16 Nov 2011 21:55:49 +0100 5408384 http://www.medworm.com/index.php?rid=5408383&cid=s_32560_13_f&fid=32560&url=http%3A%2F%2Fdx.doi.org%2F10.1111%252Fj.1476-5381.2011.01413.x CONCLUSIONS AND IMPLICATIONS Bile pigment absorption from the peritoneal and duodenal cavities demonstrate new routes of administration for the treatment of inflammatory and traumatic pathology. Oral biliverdin administration may lead to the production of active metabolite that protect from inflammation/complement activation. (Source: British Journal of Pharmacology) British Journal of Pharmacology journals http://www.medworm.com/rss/comments.php?id=5408383 Wed, 16 Nov 2011 21:55:47 +0100 5408383