Journal article

Publication year: 2009

Pages: 1263-1275

Journal: British Journal of Pharmacology

Volume number: 158

Issue number: 5

ISSN: 0007-1188

eISSN: 1476-5381

Open access status: Green

DOI Link: https://doi.org/10.1111/j.1476-5381.2009.00385.x

Publisher: Wiley

Abstract: 

Background and purpose:

The aim of this study was to identify the actions of H2S on ion transport across rat distal colon.

Experimental approach:

Changes in short-circuit current (Isc) induced by the H2S-donor, NaHS, were measured in Ussing chambers. Cytosolic Ca2+ 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 center dot 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 H2S-producing enzymes (expression demonstrated immunohistochemically) decreased basal Isc, suggesting that endogenous production of H2S 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 H2S-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 Ca2+-dependent K+ channels, suppressed NaHS-induced Cl- secretion suggesting different types of K+ channels are stimulated by the H2S-donor. NaHS-induced increase in cytosolic Ca2+ concentration was confirmed in isolated, fura-2-loaded colonic crypts. This response was not dependent on extracellular Ca2+, but was inhibited by blockers of intracellular Ca2+ channels present on Ca2+ storage organelles.

Conclusions and implications:

H2S induces colonic ion secretion by stimulation of apical as well as basolateral epithelial K+ channels.

Harvard Citation style: Hennig, B. and Diener, M. (2009) Actions of hydrogen sulphide on ion transport across rat distal colon, British Journal of Pharmacology, 158(5), pp. 1263-1275. https://doi.org/10.1111/j.1476-5381.2009.00385.x

APA Citation style: Hennig, B., & Diener, M. (2009). Actions of hydrogen sulphide on ion transport across rat distal colon. British Journal of Pharmacology. 158(5), 1263-1275. https://doi.org/10.1111/j.1476-5381.2009.00385.x