Actions of hydrogen sulphide on ion transport across rat distal colon.
OBJECTIVE
The aim of this study was to identify the actions of H(2)S on ion transport across rat distal colon.


METHODS
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.


RESULTS
NaHS concentration-dependently induced a change in Isc, that was only partially inhibited by the neurotoxin, tetrodotoxin. Lower concentrations (< or =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
H(2)S induces colonic ion secretion by stimulation of apical as well as basolateral epithelial K(+) channels.
Institute for Veterinary Physiology, Justus-Liebig-University Giessen, Giessen, Germany.
B
B
Hennig
M
M
Diener
D000818:Animals; D002118:Calcium / Q000378:metabolism; D018118:Chloride Channels / Q000502:physiology; D002712:Chlorides / Q000378:metabolism; D003106:Colon / Q000187:drug effects / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000378:metabolism*; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D017136:Ion Transport; D008297:Male; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism / Q000502:physiology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013440:Sulfides / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D018118:Chloride Channels; D002712:Chlorides; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D000644:Quaternary Ammonium Compounds; D013440:Sulfides; D013779:Tetrodotoxin; C027435:tetrapentylammonium; C025451:sodium bisulfide; D011188:Potassium; D005905:Glyburide; D002118:Calcium; D006862:Hydrogen Sulfide