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Actions of hydrogen sulphide on ion transport across rat distal colon
Author(s) -
Hennig B,
Diener M
Publication year - 2009
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2009.00385.x
Subject(s) - chemistry , extracellular , intracellular , channel blocker , secretion , cytosol , tetrodotoxin , biophysics , ion transporter , glibenclamide , medicine , biochemistry , endocrinology , enzyme , calcium , biology , membrane , organic chemistry , diabetes mellitus
Background and purpose: The aim of this study was to identify the actions of H 2 S on ion transport across rat distal colon. Experimental approach: Changes in short‐circuit current (Isc) induced by the H 2 S‐donor, NaHS, were measured in Ussing chambers. Cytosolic Ca 2+ concentration was evaluated using fura‐2. Key results: NaHS concentration‐dependently induced a change in Isc, that was only partially inhibited by the neurotoxin, tetrodotoxin. Lower concentrations (≤10 −3 mol·L −1 ) of NaHS induced a monophasic increase in Isc, whereas higher concentrations induced an additional, secondary fall of Isc, before a third phase when Isc rose again. Blockers of H 2 S‐producing enzymes (expression demonstrated immunohistochemically) decreased basal Isc, suggesting that endogenous production of H 2 S contributes to spontaneous anion secretion. The positive Isc phases induced by NaHS were due to Cl ‐ secretion as shown by anion substitution and transport inhibitor experiments, whereas the transient negative Isc induced by higher concentrations of the H 2 S‐donor was inhibited by mucosal tetrapentylammonium suggesting a transient K + secretion. When applied from the serosal side, glibenclamide, an inhibitor of ATP‐sensitive K + channels, and tetrapentylammonium, a blocker of Ca 2+ ‐dependent K + channels, suppressed NaHS‐induced Cl ‐ secretion suggesting different types of K + channels are stimulated by the H 2 S‐donor. NaHS‐induced increase in cytosolic Ca 2+ concentration was confirmed in isolated, fura‐2‐loaded colonic crypts. This response was not dependent on extracellular Ca 2+ , but was inhibited by blockers of intracellular Ca 2+ channels present on Ca 2+ storage organelles. Conclusions and implications: H 2 S induces colonic ion secretion by stimulation of apical as well as basolateral epithelial K + channels.