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The glycophorin A (GPA)-dependent, spherostomatocytosis mutant AE1 E758K induces GPA-independent, endogenous cation transport in amphibian oocytes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The previously undescribed, heterozygous missense mutation E758K was discovered in the human AE1/SLC4A1/Band 3 gene in two unrelated patients with well-compensated spherostomatocytic anemia (HSt). AE1 E758K oocyte surface expression, unlike that of wildtype AE1, required coexpressed glycophorin A (GPA). The mutant polypeptide exhibited, in parallel, strong GPA-dependence of DIDS-sensitive (36)Cl(-) influx, trans-anion-dependent (36)Cl(-) efflux, and Cl(-)/HCO(3)(-) exchange activities at near wildtype levels. AE1 E758K expression was also associated with GPA-dependent increases of DIDS-sensitive pH-independent sulfate ...
Source: American Journal of Physiology. Cell Physiology - November 11, 2009 Category: Cytology Authors: Stewart AK, Vandorpe DH, Heneghan JF, Chebib F, Stolpe K, Akhavein A, Edelman EJ, Maksimova Y, Gallagher PG, Alper SL Tags: Am J Physiol Cell Physiol Source Type: journals

Sex differences in adaptive down-regulation of pre-macula densa sodium transporters with Ang II infusion in mice.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
An increase in blood pressure (BP) due to angiotensin II (Ang II) infusion or other means is associated with adaptive pressure natriuresis due to reduced sodium reabsorption primarily in proximal tubule (PT) and thick ascending limb (TAL). We tested the hypothesis that male and female mice would show differential response to Ang II infusion with regard to the regulation of the protein abundance of sodium transporters in the PT and TAL, and whether these responses would be modulated by aging. Young (~3 months) and old (~21 months) male and female mice were infused with Ang II @ 800 ng/kg*bw/min by osmotic minimpump for ...
Source: American Journal of Physiology. Renal Physiology - November 4, 2009 Category: Physiology Authors: Tiwari S, Li L, Riazi S, Halagappa VK, Ecelbarger CM Tags: Am J Physiol Renal Physiol Source Type: journals

Hymenolepis diminuta: Effect of infection on ion transport in colon and blood picture of rats.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The aim of this study was to examine the effect of an infection with Hymenolepis diminuta on ion transport in an isolated colon and blood picture of rats. Fifty rats were orally infected with 5 cysticercoids of H. diminuta. The experimental groups of rats were assigned to four groups: group I - 8 days post-infection (dpi), group II - 16 dpi, group III - 40 dpi and group IV- 60 dpi. The control group comprised non-infected rats. The experiments consisted of measuring the transepithelial electrical potential difference (PD) and the transepithelial electrical resistance (R) of the rat colon under controlled conditions as ...
Source: Experimental Parasitology - November 3, 2009 Category: Parasitology Authors: Kosik-Bogacka DI, Baranowska-Bosiacka I, Salamatin R Tags: Exp Parasitol Source Type: journals

Activity-mediated plasticity of GABA equilibrium potential in rat hippocampal CA1 neurons.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The equilibrium potential (E(GABA-PSC)) for gamma-aminobutyric acid (GABA) A receptor mediated inhibitory postsynaptic currents (PSCs) in hippocampal CA1 pyramidal neurons shifts when theta-burst stimulation (4 pulses at 100 Hz in each burst in a train consisting of 5 bursts with an inter-burst interval of 200 ms, the train repeated thrice at 30 s intervals) is applied to the input. E(GABA-PSC) is regulated by K(+)/Cl(-)co-transporter (KCC2). GABA(B) receptors are implicated in modulating KCC2 levels. In the current study, the involvement of KCC2 as well as GABA(B) receptors in theta-burst-mediated shifts in E(GABA-PSC...
Source: Experimental Neurology - October 28, 2009 Category: Neurology Authors: Yang B, Tadavarty R, Xu JY, Sastry BR Tags: Exp Neurol Source Type: journals

Why funding epilepsy research mattersEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Last night, Frances Jensen, MD, senior associate in Neurology, was featured in a piece on 60 Minutes about the prevalence of epilepsy and the importance of funding research into its cure. Watch the piece here, then keep reading below as Jensen describes how epilepsy is often overlooked as a public health problem and how researchers like her are trying to stop it in its tracks. Also watch below as Jensen shows Katie Couric what an epilepsy looks like from a molecular perspective. Watch CBS News Videos Online By Frances Jensen, MD Last night, research by myself and my team was featured on 60 Minutes in a wonderful story abo...
Source: Thrive, Children's Hospital Boston - October 26, 2009 Category: Pediatrics Authors: Children's Hospital Boston staff Tags: All posts Bumetanide epilepsy epilepsy surgery Frances Jensen neuroscience Source Type: organizations

Frances Jensen on 60 Minutes: Why funding epilepsy research is importantEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Last night, Frances Jensen, MD, senior associate in Neurology, was featured in a piece on 60 Minutes about the prevalence of epilepsy and the importance of funding research into its cure. Watch the piece here, then keep reading below as Jensen describes how epilepsy is often overlooked as a public health problem and how researchers like her are trying to stop it in its tracks. Also watch below as Jensen shows Katie Couric what an epilepsy looks like from a molecular perspective. Watch CBS News Videos Online By Frances Jensen, MD Last night, research by myself and my team was featured on 60 Minutes in a wonderful story abo...
Source: Thrive, Children's Hospital Boston - October 26, 2009 Category: Pediatrics Authors: Children's Hospital Boston staff Tags: All posts Research at Children's Bumetanide epilepsy epilepsy surgery Frances Jensen neuroscience Source Type: organizations

Unilateral Ureteral Obstruction Alters Expression of Acid-Base Transporters in Rat KidneyEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Conclusions: The expression of renal acid-base transporters is markedly decreased in the obstructed kidney, which may be responsible for the contribution of impaired renal H+ excretion and HCO3− reabsorption to the urinary acidification defect in response to unilateral ureteral obstruction. (Source: The Journal of Urology)
Source: The Journal of Urology - October 20, 2009 Category: Urology & Nephrology Authors: Guixian Wang, Troels Ring, Chunling Li, Soo Wan Kim, Jianguo Wen, Jens Christian Djurhuus, Søren Nielsen, Jørgen Frøkiær Tags: Investigative Urology Source Type: journals

A Comprehensive Review of the Loop Diuretics: Should Furosemide Be First Line? (November)(CE).Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CONCLUSIONS: Growing evidence demonstrates more favorable pharmacokinetic profiles of torsemide and bumetanide compared with furosemide. Furthermore, torsemide may be more efficacious and safer than furosemide in patients with HF. A trial comparing all 3 drugs would be required to confirm torsemide as the primary loop diuretic in patients with HF, but based upon limited current evidence, we recommend torsemide over furosemide. Currently, little evidence exists to support either torsemide or bumetanide as first-line treatment over furosemide in patients with other edematous disease states. PMID: 19843838 [PubMed - as su...
Source: The Annals of Pharmacotherapy - October 19, 2009 Category: Drugs & Pharmacology Authors: Wargo KA, Banta WM Tags: Ann Pharmacother Source Type: journals

Developmental and functional studies of the SLC12 gene family members from Drosophila melanogaster.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The electroneutral cation-chloride cotransporter gene family, SLC12, contains nine members in vertebrates. These include seven sodium and/or potassium-coupled chloride transporters and two membrane proteins of unknown function. Although SLC12 family members have been identified in a number of lower species, the functional properties of these proteins are unknown. There are five SLC12 homologues in Drosophila melanogaster including at least one member on each of the four main branches of the vertebrate phylogenetic tree. We have employed in situ hybridization to study the expression patterns of the Drosophila SLC12 prot...
Source: American Journal of Physiology. Cell Physiology - October 13, 2009 Category: Cytology Authors: Sun Q, Tian E, Turner RJ, Ten Hagen K Tags: Am J Physiol Cell Physiol Source Type: journals

GABAergic signaling induces divergent neuronal Ca2+ responses in the suprachiasmatic nucleus networkEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Intercellular communication between [gamma]-aminobutyric acid (GABA)ergic suprachiasmatic nucleus (SCN) neurons facilitates light-induced phase changes and synchronization of individual neural oscillators within the SCN network. We used ratiometric Ca2+ imaging techniques to record changes in the intracellular calcium concentration ([Ca2+]i) to study the role of GABA in interneuronal communication and the response of the SCN neuronal network to optic nerve stimulations that mimic entraining light signals. Stimulation of the retinohypothalamic tract (RHT) evoked divergent Ca2+ responses in neurons that varied regionally wit...
Source: European Journal of Neuroscience - October 11, 2009 Category: Neuroscience Authors: Robert P. Irwin, Charles N. Allen Source Type: journals

Thrombin potentiates d-aspartate efflux from cultured astrocytes under conditions of K+ homeostasis disruptionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study examined the effect of thrombin on glutamate efflux from rat cortical cultured astrocytes using 3H-d-aspartate as radiotracer. The glutamate efflux was initiated by addition of 100 mM K+ plus 1 mM ouabain (K/O) to replicate extracellular and intracellular ionic changes that occur during cerebral ischemia. Upon exposure to K/O, astrocytes swelled slowly and progressively with no evidence of volume regulation. The K/O-induced swelling was inhibited by 65% with bumetanide and 25% with BaCl2, suggesting contribution of Na+/K+/Cl[minus] co-transporter and Kir channels. K/O-elicited 3H-d-aspartate that consisted of tw...
Source: Journal of Neurochemistry - October 3, 2009 Category: Neurology Authors: Erika Vázquez-Juárez, Reyna Hernández-Benítez, Alejandra López-Domínguez, Herminia Pasantes-Morales Source Type: journals

Chloride transport in mitochondrion-rich cells of euryhaline tilapia (Oreochromis mossambicus) larvaeEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study provides direct and convincing evidence for Cl– transport by MRCs of SW- and FW-acclimated euryhaline tilapia and the involvement of an apical NCC in Cl– uptake of MRCs of FW-acclimated fish. (Source: AJP: Cell Physiology)
Source: AJP: Cell Physiology - October 1, 2009 Category: Cytology Authors: Horng, J.-L., Hwang, P.-P., Shih, T.-H., Wen, Z.-H., Lin, C.-S., Lin, L.-Y. Tags: MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS Source Type: journals

Genistein stimulates electrogenic Cl- secretion via phosphodiesterase modulation in the mouse jejunumEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Previously, we demonstrated that genistein stimulated Cl– secretion in the mouse jejunum (Baker MJ and Hamilton KL, Am J Physiol Cell Physiol 287: C1636–C1645, 2004); however, the mode of action of genistein still remains unclear. Here, we examined the activation of Cl– secretion by the modulation of phosphodiesterases (PDEs) by genistein (75 µM) in the mouse jejunum with the Ussing short-circuit current (Isc) technique. Drugs tested included theophylline (10 mM), a nonspecific PDE inhibitor; 8-methoxymethyl-3-isobutyl-1-methylxanthine (8-MM-IBMX; 100 µM), erythro-9-(2-hydroxyl-3-nonyl)-adenin...
Source: AJP: Cell Physiology - September 4, 2009 Category: Cytology Authors: Chao, P.-C., Hamilton, K. L. Tags: MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS Source Type: journals

Excitatory GABAergic Activation of Cortical Dividing Glial CellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Adult neocortex contains dividing satellite glia population even though their characteristics and functions have still remained unknown. Nestin+/NG2+ cells as major fraction of dividing glial cells express bicuculline-sensitive -aminobutyric acid A (GABAA) receptors and receive GABAergic inputs. Due to their high [Cl–]i, GABAergic activation depolarized the cells and then induced Ca2+ influx into them. To assess an effect of this GABAergic excitation, we looked for the expression of neurotrophic factors. Among them, we detected the expression of brain-derived neurotrophic factor (BDNF) on the cells. The level of BDNF...
Source: Cerebral Cortex - August 5, 2009 Category: Neurology Authors: Tanaka, Y., Tozuka, Y., Takata, T., Shimazu, N., Matsumura, N., Ohta, A., Hisatsune, T. Tags: Articles Source Type: journals

Chloride Transport in Mitochondrion-Rich Cells of Euryhaline Tilapia (Oreochromis mossambicus) Larvae.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study provides direct and convincing evidence for Cl(-) transport by MRCs of SW- and FW-acclimated euryhaline tilapia, and the involvement of an apical NCC in Cl(-) uptake of MRCs of FW-acclimated fish. Key words: Na+-Cl- cotransporter, osmoregulation, gills, ionoregulation. PMID: 19657057 [PubMed - as supplied by publisher] (Source: American Journal of Physiology. Cell Physiology)
Source: American Journal of Physiology. Cell Physiology - August 4, 2009 Category: Cytology Authors: Horng JL, Hwang PP, Shih TH, Wen ZH, Lin CS, Lin LY Tags: Am J Physiol Cell Physiol Source Type: journals

Cerebral microvascular endothelial cell Na/H exchange: evidence for the presence of NHE1 and NHE2 isoforms and regulation by arginine vasopressinEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Blood-brain barrier (BBB) Na transporters are essential for brain water and electrolyte homeostasis. However, they also contribute to edema formation during the early hours of ischemic stroke by increased transport of Na from blood into brain across an intact BBB. We previously showed that a luminal BBB Na-K-Cl cotransporter is stimulated by hypoxia, aglycemia, and AVP and that inhibition of the cotransporter by intravenous bumetanide significantly reduces edema and infarct in the rat middle cerebral artery occlusion (MCAO) model of stroke. More recently, we found evidence that intravenous cariporide (HOE-642), a highly po...
Source: AJP: Cell Physiology - July 29, 2009 Category: Cytology Authors: Lam, T. I., Wise, P. M., O'Donnell, M. E. Tags: MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS Source Type: journals

[Small intestine] Structural and functional changes of the duodenum in human norovirus infectionEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Conclusions: Norovirus infection leads to epithelial barrier dysfunction paralleled by a reduction of sealing tight junctional proteins and an increase in epithelial apoptosis, which may partly be mediated by increased cytotoxic intraepithelial lymphocytes. Furthermore, active anion secretion is markedly stimulated. Thus, the diarrhoea in norovirus infection is driven by both a leak flux and a secretory component. (Source: Gut)
Source: Gut - July 9, 2009 Category: Gastroenterology Authors: Troeger, H, Loddenkemper, C, Schneider, T, Schreier, E, Epple, H-J, Zeitz, M, Fromm, M, Schulzke, J-D Tags: Diarrhoea Small intestine Source Type: journals

Prenatal programming of rat thick ascending limb chloride transport by low-protein diet and dexamethasoneEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This study demonstrates that insults administered to the fetus can program altered sodium transport. Increased tubular sodium transport is a likely cause for the hypertension by prenatal programming. (Source: AJP: Regulatory, Integrative and Comparative Physiology)
Source: AJP: Regulatory, Integrative and Comparative Physiology - July 1, 2009 Category: Physiology Authors: Dagan, A., Habib, S., Gattineni, J., Dwarakanath, V., Baum, M. Tags: ARTICLES Source Type: journals

An environmentally friendly reflectometric method for bumetanide determination in pharmaceuticals.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This paper describes a green analytical procedure for the determination of bumetanide using diffuse reflectance spectroscopy. The proposed method is based on reflectance measurements of a violet compound produced from a spot test reaction between bumetanide and p-dimethylaminocinnamaldehyde (p-DAC) in an acid medium, using filter paper as a solid support. The best conditions for the reaction have been found by experimental design methodologies. All reflectance measurements were carried out at 525 nm, and the linear range was from 1.37 x 10(-4) to 1.37 x 10(-3) mol L(-1), with a correlation coefficient of 0.998. The det...
Source: Analytical Sciences : the international journal of the Japan Society for Analytical Chemistry - June 30, 2009 Category: Chemistry Authors: Pollo F, Sequinel R, Rufino JL, Los Weinert P, Pezza HR, Pezza L Tags: Anal Sci Source Type: journals

Electrogenic Cl− secretion does not occur in the ileum of the Australian common brushtail possum, Trichosurus vulpecula, due to low levels of expression of the NaK2Cl cotransporter, NKCC1Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract The colon of the brushtail possum does not have an electrogenic secretory response. Given the functional significance of electrogenic Cl− secretion in the intestine of eutherian mammals, we have investigated the secretory response in the small intestine of this marsupial. In the Ussing chamber cAMP-dependent secretagogues stimulated a sustained increase in ileal short-circuit current (Isc), whereas Ca2+-dependent secretagogues induced a transient increase. Both the responses were inhibited by mucosal addition of the anion channel blocker 5-nitro-2-(3-phenylpropylamino) benzoic acid (100 μmol...
Source: Journal of Comparative Physiology B: Biochemical, Systemic, and Environmental Physiology - June 30, 2009 Category: Physiology Tags: Journal of Comparative Physiology B: Biochemical, Systemic, and Environmental Physiology Source Type: journals

The role of chloride transport in the control of the membrane potential in skeletal muscle--theory and experiment.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We present a model for the control of the transmembrane potential of mammalian skeletal muscle cell. The model involves active and passive transport of Na(+), K(+), and Cl(-). As we check the model against experimental measurements on murine skeletal muscle cells, we find that the model can account for the observed bistability of the transmembrane potential at low extracellular potassium concentration. The effect of bumetanide, a blocker of the Na,K,2Cl-cotransporter, is measured and modeled. A hyperosmotic medium is known to stimulate the Na,K,2Cl-cotransporter and we also measure and model the effects of such a medium. I...
Source: Biophysical Chemistry - June 28, 2009 Category: Chemistry Authors: Gallaher J, Bier M, Siegenbeek van Heukelom J Tags: Biophys Chem Source Type: journals

Genistein stimulates electrogenic Cl- secretion via phosphodiesterase modulation in the mouse jejunum.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Previously, we demonstrated that genistein stimulated Cl(-) secretion in the mouse jejunum (Baker and Hamilton, Am. J. Physiol. Cell Physiol. 287:C1636-C1645, 2004); however, the mode of action of genistein still remains unclear. Here, we examined the activation of Cl(-) secretion by the modulation of phosphodiesterases (PDEs) by genistein (75 microM) in the mouse jejunum with the Ussing short circuit current (Isc) technique. Drugs tested included theophylline (10 mM) a non-specific PDE inhibitor; 8-MM-IBMX (100 microM), EHNA (40 microM), milrinone (100 microM) and rolipram (40 and 100 microM), which are specific inhib...
Source: American Journal of Physiology. Cell Physiology - June 16, 2009 Category: Cytology Authors: Chao PC, Hamilton KL Tags: Am J Physiol Cell Physiol Source Type: journals

[Membrane Transport, Structure, Function, and Biogenesis] In Situ Measurement of Airway Surface Liquid [K+] Using a Ratioable K+-sensitive Fluorescent DyeEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The airway surface liquid (ASL) is the thin fluid layer lining airway surface epithelial cells, whose volume and composition are tightly regulated and may be abnormal in cystic fibrosis (CF). We synthesized a two-color fluorescent dextran to measure ASL [K+], TAC-Lime-dextran-TMR, consisting of a green-fluorescing triazacryptand K+ ionophore-Bodipy conjugate, coupled to dextran, together with a red fluorescing tetramethylrhodamine reference chromophore. TAC-Lime-dextran-TMR fluorescence was K+-selective, increasing >4-fold with increasing [K+] from 0 to 40 mm. In well differentiated human airway epithelial cells, ASL [K...
Source: Journal of Biological Chemistry - May 29, 2009 Category: Chemistry Authors: Namkung, W., Song, Y., Mills, A. D., Padmawar, P., Finkbeiner, W. E., Verkman, A. S. Tags: Membrane Transport, Structure, Function, and Biogenesis Source Type: journals

Bumetanide, an NKCC1 Antagonist, Does Not Prevent Formation of Epileptogenic Focus but Blocks Epileptic Focus Seizures in Immature Rat HippocampusEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We report that bumetanide, a NKCC1 antagonist, reduces driving force of GABA-mediated currents (DFGABA) in neonatal hippocampal neurons and blocks the giant depolarizing potentials (GDPs), a spontaneous pattern of network activity. In the preparation composed of two intact interconnected hippocampi, bumetanide did not prevent generation of kainate-induced seizures, their propagation to the contralateral hippocampus, and formation of an epileptogenic mirror focus. However, in the isolated mirror focus, bumetanide effectively blocked spontaneous epileptiform activity transforming it to the GDP-like activity pattern. Bumetani...
Source: Journal of Neurophysiology - May 26, 2009 Category: Neurology Authors: Nardou, R., Ben-Ari, Y., Khalilov, I. Tags: Articles Source Type: journals

Cerebral Microvascular Endothelial Cell Na/H Exchange: Evidence for the Presence of NHE1 and NHE2 Isoforms and Regulation by Arginine Vasopressin.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Blood-brain barrier (BBB) Na transporters are essential for brain water and electrolyte homeostasis. However, they also contribute to edema formation during the early hours of ischemic stroke through increased transport of Na from blood into brain across an intact BBB. We have shown previously that a luminal BBB Na-K-Cl cotransporter is stimulated by hypoxia, aglycemia and arginine vasopressin (AVP), and that inhibition of the cotransporter by intravenous bumetanide significantly reduces edema and infarct in the rat middle cerebral artery occlusion (MCAO) model of stroke. More recently we have found evidence that intra...
Source: American Journal of Physiology. Cell Physiology - May 19, 2009 Category: Cytology Authors: Lam TI, Wise PM, O'Donnell ME Tags: Am J Physiol Cell Physiol Source Type: journals

GABAA Receptors Mediate Excitation in Adult Rat GnRH Neurons.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In this study, we investigated the GABA-induced changes in [Ca(2+)]i of GnRH neurons from GnRH-EGFP rats both to confirm the depolarizing action of GABA and to further examine the developmental and estrous cycle-dependent modulations of GABA action. GABA increased [Ca(2+)]i in GnRH neurons in all developmental stages of both sexes. GABA also increased [Ca(2+)]i in adult female GnRH neurons prepared in the afternoon at each estrous cycle stage. The percentages of neurons with increased [Ca(2+)]i were 90% in proestrus, 59% in estrus, 84% in diestrus I, and 89% in diestrus II. In GnRH neurons prepared from adult females in th...
Source: Biology of Reproduction - April 8, 2009 Category: Reproduction Medicine Authors: Watanabe M, Sakuma Y, Kato M Tags: Biol Reprod Source Type: journals

The influence of commonly used immunosuppressive drugs on the small bowel functions - a comparative experimental study.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CONCLUSIONS: In conclusion, the analyzed immunosuppressive drugs had no direct and immediate influence on gastrointestinal function in therapeutic concentrations. However, toxic concentrations of mycophenolate mofetil, enteric coated MPA, and everolimus might be of importance for local effects on small bowel function due to oral application.<br /> <br /> <br /> PMID: 19487793 [PubMed - in process] (Source: Annals of Transplantation)
Source: Annals of Transplantation - April 1, 2009 Category: Transplant Surgery Authors: Malinowski M, Martus P, Neuhaus P, Stockmann M Tags: Ann Transplant Source Type: journals

Inhibitory actions of the gamma-aminobutyric acid in pediatric Sturge-Weber syndromeEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The mechanisms of epileptogenesis in Sturge-Weber syndrome (SWS) are unknown. We explored the properties of neurons from human pediatric SWS cortex in vitro and tested in particular whether gamma-aminobutyric acid (GABA) excites neurons in SWS cortex, as has been suggested for various types of epilepsies.Patch-clamp and field potential recordings and dynamic biphoton imaging were used to analyze cortical tissue samples obtained from four 6- to 14-month-old pediatric SWS patients during surgery.Neurons in SWS cortex were characterized by a relatively depolarized resting membrane potential, as was estimated from cell-attache...
Source: Annals of Neurology - March 26, 2009 Category: Neurology Authors: Roman Tyzio, Ilgam Khalilov, Alfonso Represa, Valerie Crepel, Yuri Zilberter, Sylvain Rheims, Laurent Aniksztejn, Rosa Cossart, Romain Nardou, Marat Mukhtarov, Marat Minlebaev, Jérôme Epsztein, Mathieu Milh, Helene Becq, Isabel Jorquera, Christine Bulte Source Type: journals

Abundance of the Na-K-2Cl cotransporter NKCC2 is increased by high-fat feeding in Fischer 344 X Brown Norway (F1) ratsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Insulin resistance is associated with hypertension by mechanisms likely involving the kidney. To determine how the major apical sodium transporter of the thick ascending limb, the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) is regulated by high-fat feeding, we treated young male, Fischer 344 X Brown Norway (F344BN) rats for 8 wk with diets containing either normal (NF, 4%) or high (HF, 36%) fat, by weight, primarily as lard. HF-fed rats had impaired glucose tolerance, increased urine excretion of 8-isoprostane (a marker of oxidative stress), increased protein levels for NKCC2 (50–125%) and the renal outer med...
Source: AJP: Renal Physiology - March 20, 2009 Category: Urology & Nephrology Authors: Riazi, S., Tiwari, S., Sharma, N., Rash, A., Ecelbarger, C. M. Tags: ARTICLES Source Type: journals

Low salt concentrations activate AMP-activated protein kinase in mouse macula densa cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The energy-sensing kinase AMP-activated protein kinase (AMPK) is associated with the sodium-potassium-chloride cotransporter NKCC2 in the kidney and phosphorylates it on a regulatory site in vitro. To identify a potential role for AMPK in salt sensing at the macula densa, we have used the murine macula densa cell line MMDD1. In this cell line, AMPK was rapidly activated by isosmolar low-salt conditions. In contrast to the known salt-sensing pathway in the macula densa, AMPK activation occurred in the presence of either low sodium or low chloride and was unaffected by inhibition of NKCC2 with bumetanide. Assays using recomb...
Source: AJP: Renal Physiology - March 20, 2009 Category: Urology & Nephrology Authors: Cook, N., Fraser, S. A., Katerelos, M., Katsis, F., Gleich, K., Mount, P. F., Steinberg, G. R., Levidiotis, V., Kemp, B. E., Power, D. A. Tags: ARTICLES Source Type: journals

[Mechanisms Of Signal Transduction] Nerve Terminal GABAA Receptors Activate Ca2+/Calmodulin-dependent Signaling to Inhibit Voltage-gated Ca2+ Influx and Glutamate ReleaseEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
-Aminobutyric acid type A (GABAA) receptors, a family of Cl--permeable ion channels, mediate fast synaptic inhibition as postsynaptically enriched receptors for -aminobutyric acid at GABAergic synapses. Here we describe an alternative type of inhibition mediated by GABAA receptors present on neocortical glutamatergic nerve terminals and examine the underlying signaling mechanism(s). By monitoring the activity of the presynaptic CaM kinase II/synapsin I signaling pathway in isolated nerve terminals, we demonstrate that GABAA receptor activation correlated with an increase in basal intraterminal [Ca2+]i. Interestingly, this ...
Source: Journal of Biological Chemistry - March 20, 2009 Category: Chemistry Authors: Long, P., Mercer, A., Begum, R., Stephens, G. J., Sihra, T. S., Jovanovic, J. N. Tags: Mechanisms Of Signal Transduction Source Type: journals

Expression levels of the alpha4 subunit of the GABA(A) receptor in differentiated neuroblastoma cells are correlated with GABA-gated current.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The alpha4 subunit of the GABA(A) receptor (GABAR) is capable of rapid plasticity, increased by chronic exposure to positive GABA modulators, such as the neurosteroid 3alpha-OH-5alpha[beta]-pregnan-20-one (THP). Here, we show that 48 h exposure of differentiated neuroblastoma cells (IMR-32) to 100 nM THP increases alpha4 expression, without changing the current density or the concentration-response curve. Increased expression of alpha4-containing GABAR was verified by a relative insensitivity of GABA (EC(20))-gated current to modulation by the benzodiazepine (BZ) lorazepam (0.01 - 100 muM), and potentiation of current ...
Source: Neuropharmacology - March 10, 2009 Category: Drugs & Pharmacology Authors: Zhou X, Smith SS Tags: Neuropharmacology Source Type: journals

Quercetin Stimulates Na+/K+/2Cl- Cotransport via PTK-dependent Mechanisms in Human Airway Epithelium.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
We investigated regulatory mechanisms of Cl- secretion playing an essential role in maintenance of surface fluid in human airway epithelial Calu-3 cells. The present study reports that quercetin (a flavonoid) stimulated bumetanide-sensitive Cl- secretion with reduction of apical Cl- conductance, suggesting that quercetin stimulates Cl- secretion by activating an entry step of Cl- across the basolateral membrane through Na(+)/K(+)/2Cl(-) cotransporter (NKCC1). To clarify the stimulatory mechanism of NKCC1 by quercetin, we verified involvement of PKA, PKC, PTK and cytosolic Ca2+-dependent pathways. A PKA inhibitor (PKI-1...
Source: Am J Respir Cell Mol... - February 27, 2009 Category: Respiratory Medicine Authors: Asano J, Niisato N, Nakajima KI, Miyazaki H, Yasuda M, Iwasaki Y, Hama T, Dejima K, Hisa Y, Marunaka Y Tags: Am J Respir Cell Mol Biol Source Type: journals

Bumetanide inhibits rapid kindling in neonatal rats.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Discussion: The obtained results provide further evidence that bumetanide may be beneficial for treating neonatal seizures, and that NKCC1 represents a potential target for antiepileptic interventions in the immature brain. PMID: 19260939 [PubMed - as supplied by publisher] (Source: Epilepsia)
Source: Epilepsia - February 26, 2009 Category: Neurology Authors: Mazarati A, Shin D, Sankar R Tags: Epilepsia Source Type: journals

NH(4)(+) Secretion in the Avian Colon. An actively regulated barrier to ammonium permeation of the colon mucosa.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Experiments were designed to characterize an active, electrogenic transport of NH(4)(+) ions across the colonic epithelium of the domestic fowl (Gallus gallus). Colonic segments were isolated and stripped of underlying muscle. The mucosal epithelia were mounted in Ussing chambers and voltage-clamped to measure the short-circuit currents (I(SC)) associated with transport. Bilateral addition of NH(4)(+) caused a dose-dependent outward current (negative I(SC)), with a Km of 34+8 mM and a maximal current response of 311+47 microA cm(-2) (12+2 microEq cm(-2) h(-1)). A similar effect was seen with unilateral addition of NH(4...
Source: Comparative Biochemistry and Physiology. Part A, Molecular and integrative physiology. - February 25, 2009 Category: Physiology Authors: Holtug K, Laverty G, Arnason SS, Skadhauge E Tags: Comp Biochem Physiol A Mol Integr Physiol Source Type: journals

HCO (3) (-) -dependent volume regulation in alpha-cells of the rat endocrine pancreas.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Ion transport activity in pancreatic alpha-cells was assessed by studying cell volume regulation in response to anisotonic solutions. Cell volume was measured by a video imaging method, and cells were superfused with either 4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid-buffered or HCO (3) (-) -buffered solutions. alpha-Cells did not exhibit a regulatory volume increase (RVI) in response to cell shrinkage caused by hypertonic solutions. A RVI was observed, however, in cells that had first undergone a regulatory volume decrease (RVD), but only in HCO (3) (-) -buffered solutions. RVI was also observed in response to ...
Source: Pflugers Archiv : European Journal of Physiology - February 13, 2009 Category: Physiology Authors: Davies SL, Best L, Brown PD Tags: Pflugers Arch Source Type: journals

F.D.A. Finds ‘Natural’ Diet Pills Laced With DrugsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The Food and Drug Administration says the weight-loss capsules StarCaps contain a potent pharmaceutical drug called bumetanide, which can have serious side effects. (Source: NYT)
Source: NYT - February 10, 2009 Category: American Health Authors: By NATASHA SINGER Tags: Food and Drug Administration Dietary Supplements and Herbal Remedies Recalls and Bans of Products StarCaps Source Type: news

Dangerous Secret in Diet PillsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The Food Drug Administration says the weight-loss capsules StarCaps contain a potent pharmaceutical drug called bumetanide, which can have serious side effects. (Source: NYT > Health)
Source: NYT > Health - February 10, 2009 Category: Consumer Health News Authors: By NATASHA SINGER Tags: Food and Drug Administration Dietary Supplements and Herbal Remedies Recalls and Bans of Products StarCaps Source Type: news

Presynaptic glycine receptors facilitate spontaneous glutamate release onto hilar neurons in the rat hippocampus.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Although glycine receptors are found in most areas of the brain, including the hippocampus, their functional significance remains largely unknown. In the present study, we have investigated the role of presynaptic glycine receptors on excitatory nerve terminals in spontaneous glutamatergic transmission. Spontaneous EPSCs (sEPSCs) were recorded in mechanically dissociated rat dentate hilar neurons attached with native presynaptic nerve terminals using a conventional whole-cell patch recording technique under voltage-clamp conditions. Exogenously applied glycine or taurine significantly increased the frequency of sEPSCs ...
Source: Journal of Neurochemistry - February 5, 2009 Category: Neurology Authors: Lee EA, Cho JH, Choi IS, Nakamura M, Park HM, Lee JJ, Lee MG, Choi BJ, Jang IS Tags: J Neurochem Source Type: journals

The abundance of the Na-K-2Cl cotransporter (NKCC2) is increased by high-fat feeding in Fisher 344 X Brown Norway (F1) rats.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Insulin resistance is associated with hypertension by mechanisms likely involving the kidney. To determine how the major apical sodium transporter of the thick ascending limb (TAL), the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) is regulated by high-fat feeding, we treated young male, Fisher 344 X Brown Norway (F344BN) rats for 8 weeks with diets containing either normal- (NF, 4%) or high- (HF, 36%) fat, by weight, primarily as lard. HF-fed rats had impaired glucose tolerance, increased urine excretion of 8-isoprostane (a marker of oxidative stress), increased protein levels for NKCC2 (50-125%) and the renal o...
Source: American Journal of Physiology. Renal Physiology - February 4, 2009 Category: Physiology Authors: Riazi S, Tiwari S, Sharma N, Rash A, Ecelbarger CM Tags: Am J Physiol Renal Physiol Source Type: journals

The multi-herbal drug STW 5 (Iberogast®) has prosecretory action in the human intestineEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Abstract There is growing evidence that STW 5 (Iberogast®, fixed combination of hydroethanolic herbal extracts), besides being effective in functional dyspepsia, also improves symptoms in irritable bowel syndrome (IBS). Clinical data indicate that modulation of mucosal secretion is a promising approach to treat intestinal disorders associated with IBS. We therefore explored the effect of STW 5 on secretion in the human intestine and the mechanisms by which it acts. The Ussing chamber technique was used to measure mucosal secretion in human intestinal mucosa/submucosa preparations and in human epithelial cell line T84. In ...
Source: Neurogastroenterology and Motility - February 3, 2009 Category: Gastroenterology Authors: d. krueger, l. gruber, s. buhner, f. zeller, r. langer, s. seidl, k. michel, m. schemann Source Type: journals

Low salt concentrations activate AMP-activated protein kinase in mouse macula densa cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The energy-sensing kinase AMP-activated protein kinase (AMPK) is associated with the sodium co-transporter NKCC2 in the kidney, and phosphorylates it on a regulatory site in vitro. To identify a potential role for AMPK in salt sensing at the macula densa, we have used the murine macula densa cell line MMDD1. In this cell line, AMPK was rapidly activated by iso-osmolar low salt conditions. In contrast to the known salt-sensing pathway in the macula densa, AMPK activation occurred in the presence of either low sodium or low chloride, and was unaffected by inhibition of NKCC2 with bumetanide. Assays using recombinant AMPK...
Source: American Journal of Physiology. Renal Physiology - January 28, 2009 Category: Physiology Authors: Cook N, Fraser SA, Katerelos M, Katsis F, Gleich K, Mount PF, Steinberg GR, Levidiotis V, Kemp BE, Power DA Tags: Am J Physiol Renal Physiol Source Type: journals

cAMP-dependent chloride secretion mediates tubule enlargement and cyst formation by cultured mammalian collecting duct cellsEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Polycystic kidney diseases result from disruption of the genetically defined program that controls the size and geometry of renal tubules. Cysts which frequently arise from the collecting duct (CD) result from cell proliferation and fluid secretion. From mCCDcl1 cells, a differentiated mouse CD cell line, we isolated a clonal subpopulation (mCCD-N21) that retains morphogenetic capacity. When grown in three-dimensional gels, mCCD-N21 cells formed highly organized tubular structures consisting of a palisade of polarized epithelial cells surrounding a cylindrical lumen. Subsequent addition of cAMP-elevating agents (forskolin ...
Source: AJP: Renal Physiology - January 26, 2009 Category: Urology & Nephrology Authors: Montesano, R., Ghzili, H., Carrozzino, F., Rossier, B. C., Feraille, E. Tags: INNOVATIVE METHODOLOGY Source Type: journals

Random Stimulation of Spider Mechanosensory Neurons Reveals Long-Lasting Excitation by GABA and MuscimolEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
-Aminobutyric acid type A (GABAA) receptor activation inhibits many primary afferent neurons by depolarization and increased membrane conductance. Deterministic (step and sinusoidal) functions are commonly used as stimuli to test such inhibition. We found that when the VS-3 mechanosensory neurons innervating the spider lyriform slit-sense organ were stimulated by randomly varying white-noise mechanical or electrical signals, their responses to GABAA receptor agonists were more complex than the inhibition observed during deterministic stimulation. Instead, there was rapid excitation, then brief inhibition, followed by long-...
Source: Journal of Neurophysiology - January 13, 2009 Category: Neurology Authors: Pfeiffer, K., Panek, I., Hoger, U., French, A. S., Torkkeli, P. H. Tags: Articles Source Type: journals

Excitation-contraction coupling in resistance mesenteric arteries: Evidence for NKCC1-mediated pathway.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Bumetanide and other high-ceiling diuretics (HCD) attenuate myogenic tone and contractions of vascular smooth muscle cells (VSMC) triggered by diverse stimuli. HCD outcome may be mediated by their interaction with NKCC1, the only isoform of Na(+), K(+), 2Cl(-) cotransporter expressed in VSMC as well as with targets distinct from this carrier. To examine these hypotheses, we compared the effect of bumetanide on contractions of mesenteric arteries from wild-type and NKCC1 knockout mice. In mesenteric arteries from wild-type controls, 100muM bumetanide evoked a decrease of up to 4-fold in myogenic tone and contractions tr...
Source: Biochemical and Biophysical Research communications - January 13, 2009 Category: Biochemistry Authors: Koltsova SV, Kotelevtsev SV, Tremblay J, Hamet P, Orlov SN Tags: Biochem Biophys Res Commun Source Type: journals

To Depolarize or Hyperpolarize? At the Axon Initial Segment, EGABA Sets the StageEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
GABAergic Depolarization of the Axon Initial Segment in Cortical Principal Neurons Is Caused by the Na-K-2Cl Cotransporter NKCC1. Khirug S, Yamada J, Afzalov R, Voipio J, Khiroug L, Kaila K. J Neurosci. 2008;28(18):4635[ndash]4639. GABAergic terminals of axo-axonic cells (AACs) are exclusively located on the axon initial segment (AIS) of cortical principal neurons, and they are generally thought to exert a powerful inhibitory action. However, recent work (Szabadics et al., 2006) indicates that this input from AACs can be depolarizing and even excitatory. Here, we used local photolysis of caged GABA to measure reversal pote...
Source: Epilepsy Currents - January 7, 2009 Category: Neurology Tags: Current Literature in BASIC SCIENCE Source Type: journals

[Mechanisms Of Signal Transduction] Chloride Is Essential for Capacitation and for the Capacitation-associated Increase in Tyrosine PhosphorylationEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
After epididymal maturation, sperm capacitation, which encompasses a complex series of molecular events, endows the sperm with the ability to fertilize an egg. This process can be mimicked in vitro in defined media, the composition of which is based on the electrolyte concentration of the oviductal fluid. It is well established that capacitation requires Na+, HCO3-, Ca2+, and a cholesterol acceptor; however, little is known about the function of Cl– during this important process. To determine whether Cl–, in addition to maintaining osmolarity, actively participates in signaling pathways that regulate capacitati...
Source: Journal of Biological Chemistry - December 12, 2008 Category: Chemistry Authors: Wertheimer, E. V., Salicioni, A. M., Liu, W., Trevino, C. L., Chavez, J., Hernandez-Gonzalez, E. O., Darszon, A., Visconti, P. E. Tags: Mechanisms Of Signal Transduction Source Type: journals

Does the intracellular ionic concentration or the cell water content (cell volume) determine the activity of TonEBP in NIH3T3 cells?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The transcription factor, tonicity-responsive enhancer binding protein (TonEBP), is involved in the adaptive response against hypertonicity. TonEBP regulates the expression of genes that catalyze the accumulation of osmolytes, and its transcriptional activity is increased by hypertonicity. The goal of the present investigation was to investigate whether cell shrinkage or high intracellular ionic concentration induced the activation of TonEBP. We designed a model system for isotonically shrinking cells over a prolonged period of time. Cells swelled in hypotonic medium and performed a regulatory volume decrease. Upon return ...
Source: AJP: Cell Physiology - December 5, 2008 Category: Cytology Authors: Rodgaard, T., Schou, K., Friis, M. B., Hoffmann, E. K. Tags: GROWTH, DIFFERENTIATION, AND APOPTOSIS Source Type: journals

Cyclic AMP-dependent Chloride Secretion Mediates Tubule Enlargement and Cyst Formation by Cultured Mammalian Collecting Duct Cells.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Polycystic kidney diseases result from disruption of the genetically defined program that controls the size and geometry of renal tubules. Cysts which frequently arise from the collecting duct (CD) result from cell proliferation and fluid secretion. From mCCDcl1 cells, a differentiated mouse CD cell line, we isolated a clonal subpopulation (mCCD-N21) that retains morphogenetic capacity. When grown in three-dimensional gels, mCCD-N21 cells formed highly organized tubular structures consisting of a palisade of polarized epithelial cells surrounding a cylindrical lumen. Subsequent addition of cAMP-elevating agents (forsko...
Source: American Journal of Physiology. Renal Physiology - December 3, 2008 Category: Physiology Authors: Montesano R, Ghzili H, Carrozzino F, Rossier BC, Feraille E Tags: Am J Physiol Renal Physiol Source Type: journals

Ammonium-evoked alterations in intracellular sodium and pH reduce glial glutamate transport activityEmail this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The clearance of extracellular glutamate is mainly mediated by pH- and sodium-dependent transport into astrocytes. During hepatic encephalopathy (HE), however, elevated extracellular glutamate concentrations are observed. The primary candidate responsible for the toxic effects observed during HE is ammonium (NH4+/NH3). Here, we examined the effects of NH4+/NH3 on steady-state intracellular pH (pHi) and sodium concentration ([Na+]i) in cultured astrocytes in two different age groups. Moreover, we assessed the influence of NH4+/NH3 on glutamate transporter activity by measuring D-aspartate-induced pHi and [Na+]i transients. ...
Source: Glia - December 2, 2008 Category: Neurology Authors: Tony Kelly, Karl W. Kafitz, Claudia Roderigo, Christine R. Rose Source Type: journals