Actions of Hydrogen Sulfide and ATP-Sensitive Potassium Channels on Colonic Hypermotility in a Rat Model of Chronic Stress

OBJECTIVE: To investigate the potential role of hydrogen sulphide (H(2)S) and ATP-sensitive potassium (K(ATP)) channels in chronic stress-induced colonic hypermotility. METHODS: Male Wistar rats were submitted daily to 1 h of water avoidance stress (WAS) or sham WAS (SWAS) for 10 consecutive days. Organ bath recordings, H(2)S production, immunohistochemistry and western blotting were performed on rat colonic samples to investigate the role of endogenous H(2)S in repeated WAS-induced hypermotility. Organ bath recordings and western blotting were used to detect the role of K(ATP) channels in repeated WAS. RESULTS: Repeated WAS increased the number of fecal pellets per hour and the area under the curve of the spontaneous contractions of colonic strips, and decreased the endogenous production of H(2)S and the expression of H(2)S-producing enzymes in the colon devoid of mucosa and submucosa. Inhibitors of H(2)S-producing enzymes increased the contractile activity of colonic strips in the SWAS rats. NaHS concentration-dependently inhibited the spontaneous contractions of the strips and the NaHS IC(50) for the WAS rats was significantly lower than that for the SWAS rats. The inhibitory effect of NaHS was significantly reduced by glybenclamide. Repeated WAS treatment resulted in up-regulation of Kir6.1 and SUR2B of K(ATP) channels in the colon devoid of mucosa and submucosa. CONCLUSION: The colonic hypermotility induced by repeated WAS may be associated with the decreased production of endogenous H(2)S. The increased expression of the subunits of K(ATP) channels in colonic smooth muscle cells may be a defensive response to repeated WAS. H(2)S donor may have potential clinical utility in treating chronic stress- induced colonic hypermotility.