H2 S modulates duodenal motility in male rats via activating TRPV1 and K(ATP) channels

Br J Pharmacol. 2014 Mar;171(6):1534-50. doi: 10.1111/bph.12562.


Background and purpose: H2 S induces vasodilatation by opening KATP channels but it may also affect other ion channels. The aim of this study was to investigate the effect of H2 S on intestinal motility in rats and its underlying mechanism.

Experimental approach: The tension of intestinal muscle strips, afferent firing of intestinal mesenteric nerves, length of duodenal smooth muscle cells and whole-cell membrane potential of dorsal root ganglion (DRG) neurons were monitored. H2 S-producing enzymes were located by immunofluorescence staining.

Key results: NaHS exerted early transient excitation and late long-lasting inhibition on the intestinal contraction. The excitation was attenuated by TRPV1 antagonists capsazepine, A784168, SB-366791 and NK1 receptor antagonist L703606, while the inhibition was attenuated by glibenclamide. NaHS increased duodenal afferent nerve firing and depolarized DRG neurons. These effects were reduced by capsazepine and A784168. NaHS relaxed isolated duodenal smooth muscle cells. The KATP channels were expressed in smooth muscle cells. Cystathionine β-synthase and cystathionine γ-lyase were expressed in rat duodenal myenteric neurons. L-cysteine and S-adenosyl-L-methionine increased the contraction of duodenal muscle strips, an effect attenuated by capsazepine and L703606.

Conclusions and implications: NaHS induces biphasic effects on intestinal motility in rats while endogenous H2 S only exerts an excitatory effect. This transient excitatory effect might be mediated by activation of TRPV1 channels in sensory nerve terminals with the consequent release of substance P. The long-lasting inhibitory effect might be mediated by activation of KATP channels in the smooth muscle cells. These findings reveal a novel mechanism for the excitatory effect of H2 S on gastrointestinal motility.

Keywords: H2S; KATP; TRPV1; duodenum; motility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Duodenum / drug effects*
  • Duodenum / innervation
  • Duodenum / physiology
  • Ganglia, Spinal / cytology
  • Gastrointestinal Motility / drug effects*
  • Hydrogen Sulfide / pharmacology*
  • In Vitro Techniques
  • Male
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology
  • Patch-Clamp Techniques
  • Rats
  • Rats, Wistar


  • Hydrogen Sulfide