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Anion Secretion (anion + secretion)

Distribution by Scientific Domains

Medical Sciences	50%

Selected Abstracts

Role of mitogen-activated protein kinases in tauroursodeoxycholic acid-induced bile formation in cholestatic rat liver

HEPATOLOGY RESEARCH, Issue 7 2008
Gerald Ulrich Denk
Aim:, Ursodeoxycholic acid exerts anticholestatic effects in various cholestatic disorders and experimental models of cholestasis. Its taurine conjugate (TUDCA) stimulates bile salt secretion in isolated perfused rat livers (IPRL) under physiological, non-cholestatic conditions, in part by mitogen-activated protein kinase (MAPK)-dependent mechanisms. The role of MAPK in the anticholestatic effect of TUDCA, however, is unclear. Therefore, we studied the role of MAPK in the anticholestatic effect of TUDCA in IPRL and isolated rat hepatocytes (IRH) in taurolithocholic acid (TLCA)-induced cholestasis. Methods:, Bile flow, biliary levels of 2,4-dinitrophenyl-S-glutathione (GS-DNP) as a marker of hepatobiliary organic anion secretion and activity of lactate dehydrogenase (LDH) in hepatovenous effluate as a marker of hepatocellular damage in IPRL perfused with TUDCA and/or TLCA were determined in the presence or absence of MAPK inhibitors. In addition, phosphorylation of Erk 1/2 and p38MAPK induced by TUDCA and/or TLCA was studied by Western immunoblot in IPRL and IRH. Results:, TUDCA-induced bile flow was impaired by the Erk 1/2 inhibitor PD98059 in normal livers (,28%), but not in livers made cholestatic by TLCA. GS-DNP secretion was unaffected by PD98059 under both conditions. TUDCA-induced bile formation and organic anion secretion both in the presence and absence of TLCA were unaffected by the p38MAPK inhibitor SB202190. Erk 1/2 phosphorylation in liver tissue was unchanged after bile salt exposure for 70 min, but was transiently enhanced by TUDCA in IRH. Conclusion:, MAPK do not mediate the anticholestatic effects of TUDCA in TLCA-induced cholestasis. [source]

Diverse transport modes by the solute carrier 26 family of anion transporters

THE JOURNAL OF PHYSIOLOGY, Issue 10 2009
Ehud Ohana
The solute carrier 26 (SLC26) transporters are anion transporters with diverse substrate specificity. Several members are ubiquitous while others show limited tissue distribution. They are expressed in many epithelia and to the extent known, play a central role in anion secretion and absorption. Members of the family are primarily Cl, transporters, although some members transport mainly SO42,, Cl,, HCO3, or I,. A defining feature of the family is their functional diversity. Slc26a1 and Slc26a2 function as specific SO42, transporters while Slc26a4 functions as an electroneutral Cl,/I,/HCO3, exchanger. Slc26a3 and Slc26a6 function as coupled electrogenic Cl,/HCO3, exchangers or as bona fide anion channels. SLC26A7 and SLC26A9 function exclusively as Cl, channels. This short review discusses the functional diversity of the SLC26 transporters. [source]

Apical SK potassium channels and Ca2+ -dependent anion secretion in endometrial epithelial cells

THE JOURNAL OF PHYSIOLOGY, Issue 3 2008
Melissa L. Palmer
Apical uridine triphosphate (UTP) stimulation was shown to increase short circuit current (Isc) in immortalized porcine endometrial gland epithelial monolayers. Pretreatment with the bee venom toxin apamin enhanced this response. Voltage-clamp experiments using amphotericin B-permeablized monolayers revealed that the apamin-sensitive current increased immediately after UTP stimulation and was K+ dependent. The current,voltage relationship was slightly inwardly rectifying with a reversal potential of ,52 ± 2 mV, and the PK/PNa ratio was 14, indicating high selectivity for K+. Concentration,response relationships for apamin and dequalinium had IC50 values of 0.5 nm and 1.8 ,m, respectively, consistent with data previously reported for SK3 channels in excitable cells and hepatocytes. Treatment of monolayers with 50 ,m BAPTA-AM completely blocked the effects of UTP on K+ channel activation, indicating that the apamin-sensitive current was also Ca2+ dependent. Moreover, channel activation was blocked by calmidazolium (IC50= 5 ,m), suggesting a role for calmodulin in Ca2+ -dependent regulation of channel activity. RT-PCR experiments demonstrated expression of mRNA for the SK1 and SK3 channels, but not SK2 channels. Treatment of monolayers with 20 nm oestradiol-17, produced a 2-fold increase in SK3 mRNA, a 2-fold decrease in SK1 mRNA, but no change in GAPDH mRNA expression. This result correlated with a 2.5-fold increase in apamin-sensitive K+ channel activity in the apical membrane. We speculate that SK channels provide a mechanism for rapidly sensing changes in intracellular Ca2+ near the apical membrane, evoking immediate hyperpolarization necessary for increasing the driving force for anion efflux following P2Y receptor activation. [source]

The regulation of veratridine-stimulated electrogenic ion transport in mouse colon by neuropeptide Y (NPY), Y1 and Y2 receptors

BRITISH JOURNAL OF PHARMACOLOGY, Issue 5 2005
Niall P Hyland
Neuropeptide Y (NPY) is a prominent enteric neuropeptide with prolonged antisecretory effects in mammalian intestine. Veratridine depolarises neurons consequently causing epithelial anion secretion across mouse colon mucosa. Our aim was to characterise functionally, veratridine-stimulated mucosal responses and to determine the roles for NPY, Y1, and Y2 receptors in modulating these neurogenic effects. Colon mucosae (with intact submucous innervation) from wild-type mice (+/+) and knockouts lacking either NPY (NPY,/,), Y1,/, or Y2,/, were placed in Ussing chambers and voltage clamped at 0 mV. Veratridine-stimulated short-circuit current (Isc) responses in +/+, Y1 or Y2 antagonist pretreated +/+ colon, Y1,/, and NPY,/, colon were insensitive to cholinergic blockade by atropine (At; 1 ,M) and hexamethonium (Hex; 10 ,M). Tetrodotoxin (TTX, 100 nM) abolished veratridine responses, but had no effect upon carbachol (CCh) or vasoactive intestinal polypeptide (VIP)-induced secretory responses. To establish the functional roles for Y1 and Y2 receptors, +/+ tissues were pretreated with either the Y1 or Y2 receptor antagonist (BIBO3304 (300 nM) or BIIE0246 (1 ,M), respectively) and veratridine responses were compared with those from Y1,/, or Y2,/, colon. Neither BIBO3304 nor Y1,/, altered veratridine-induced secretion, but Y1 agonist responses were abolished in both preparations. In contrast, the Y2 antagonist BIIE0246 significantly amplified veratridine responses in +/+ mucosa. Unexpectedly, NPY,/, colon exhibited significantly attenuated veratridine responses (between 1 and 5 min). We demonstrate that electrogenic veratridine responses in mouse colon are noncholinergic and that NPY can act directly upon epithelia, a Y1 receptor effect. The enhanced veratridine response observed in +/+ tissue following BIIE0246, indicates that Y2 receptors are located on submucosal neurons and that their activation by NPY will inhibit enteric noncholinergic secretory neurotransmission. We also demonstrate Y1 and Y2 receptor-mediated antisecretory tone in +/+ colon and show selective loss of each in Y1 and Y2 null colon respectively. In NPY,/, tissue, only Y1 -mediated tone was present, this presumably being mediated by endogenous endocrine peptide YY. Y2 tone was absent from NPY,/, (and Y2,/,) colon and we conclude that NPY activation of neuronal Y2 receptors attenuates secretory neurotransmission thereby providing an absorptive electrolyte tone in isolated colon. British Journal of Pharmacology (2005) 146, 712,722. doi:10.1038/sj.bjp.0706368 [source]