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

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.

Altered Microbiota Composition Mediates Depressive Behavior During Chronic Stress

“…We therefore turned to our alternative hypothesis, of altered intestinal physiology mediating the microbiota changes. Similarly to previous reports using stress models 159,160 , intestinal motility was significantly increased in the stressed animals ( Fig. 6a).…”

Synthesis of H2S in the Gastrointestinal Tract

“…Since glibenclamide and L-NAME, a nitric oxide synthase, did not affect the NaHS-induced inhibition, so that KATP channel and NO were not involved in the effect [49] . In the rat and human colon, NaHS also inhibited the colonic motility [45,50,51] . Interestingly, H2S exhibited different effects on different colonic motility patterns, for example, NaHS inhibited rhythmic propulsive motor complexes (RPMCs) which is associated with outflow, but enhanced the amplitude of ripples which may be associated with promoting mixing.…”

“…Interestingly, H2S exhibited different effects on different colonic motility patterns, for example, NaHS inhibited rhythmic propulsive motor complexes (RPMCs) which is associated with outflow, but enhanced the amplitude of ripples which may be associated with promoting mixing. The inhibitory effect of NaHS on the colonic motility was reduced by KATP channel blocker and small conductance calcium-activated potassium channel (SKCa) blocker, which suggest that both KATP and SKCa channels are involved in the effect [45,50,51] .…”

“…We can summarize the mechanism of H2S in regulation of gastrointestinal motility as below: (1) H2S can affect enteric neurons. H2S can activate TRPV1 channel in the primary afferent neurons to release a neurotransmitter [27,41] , or H2S can affect the cholinergic neuromuscular transmission [46,50] to regulate the smooth muscle motility; (2) H2S can directly influence the channels in the smooth muscle cells, such as KATP channel [27,39,41,45,47,50,51] , voltage-dependent K + channel [23,39] and SKCa channel [45,47,50] . However, it is not clear how H2S affect these channels.…”

Carbon Monoxide, Hydrogen Sulfide, and Nitric Oxide as Signaling Molecules in the Gastrointestinal Tract

“…In a recent study investigating the potential role of H 2 S and K ATP channels, placing rats in a water avoidance stress test, which increased colonic motility, was found to increase expression of the pore-forming Kir6.1 and SUR2B subunits. 110 Although K ATP channels appear to be regulated by H 2 S during mucosal secretion and in smooth muscle and visceral afferents, it is not clear whether sulfhydration is a form of cell signaling or a reversible process.…”