Abstract
ObjectiveTo investigate the potential role of hydrogen sulphide (H2S) and ATP-sensitive potassium (KATP) channels in chronic stress-induced colonic hypermotility.MethodsMale Wistar rats were submitted daily to 1 h of water avoidance stress (WAS) or sham WAS (SWAS) for 10 consecutive days. Organ bath recordings, H2S production, immunohistochemistry and western blotting were performed on rat colonic samples to investigate the role of endogenous H2S in repeated WAS-induced hypermotility. Organ bath recordings and western blotting were used to detect the role of KATP channels in repeated WAS.ResultsRepeated 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 H2S and the expression of H2S-producing enzymes in the colon devoid of mucosa and submucosa. Inhibitors of H2S-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 IC50 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 KATP channels in the colon devoid of mucosa and submucosa.ConclusionThe colonic hypermotility induced by repeated WAS may be associated with the decreased production of endogenous H2S. The increased expression of the subunits of KATP channels in colonic smooth muscle cells may be a defensive response to repeated WAS. H2S donor may have potential clinical utility in treating chronic stress- induced colonic hypermotility.
Highlights
Different psychological and environmental stressors affect physiologic functions of the gastrointestinal tract and play important roles in the pathophysiology of gastrointestinal diseases [1]
To identify whether alteration in smooth muscle level contributes to the changes of colonic contractile response, colon segments were pretreated with tetrodotoxin (TTX) in organ bath for 30 min in order to block the inuence of the enteric nervous system on smooth muscle contractions
H2S Synthesis was Decreased Following Repeated water avoidance stress (WAS) The level of H2S produced by the colonic tissue devoid of mucosa and submucosa in the WAS rats was decreased, as compared with that in the sham WAS (SWAS) rats (8.8561.63 nmol?min21?g21 vs. 13.2961.72 nmol?min21?g21 tissue, n = 10/group, P,0.001, Figure 3)
Summary
Different psychological and environmental stressors affect physiologic functions of the gastrointestinal tract and play important roles in the pathophysiology of gastrointestinal diseases [1]. Hydrogen sulfide (H2S) has recently been identified as a new ‘‘gasotransmitter’’. It is synthesized in many mammalian tissues and produces effects on various biological targets that have widespread consequences, ranging from cytotoxic to cytoprotective [9]. Cystathionine b-synthase (CBS) and systathionine c-lyase (CSE) are two important enzymes for generation of endogenous H2S [9]. They have been shown to be expressed in the smooth muscle cells, enteric neurons, interstitial cells of Cajal, and epithelial cells of the gastrointestinal (GI) tract [10]. Pharmacological studies show that exogenously applied NaHS, a H2S donor, inhibits gastric and intestinal motility, causing GI smooth muscle relaxation [13,14,15,16,17]
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