Mechanisms of action of the gasotransmitter hydrogen sulfide in modulating contractile activity of longitudinal muscle of rat ileum

J Gastrointest Surg. 2011 Jan;15(1):12-22. doi: 10.1007/s11605-010-1306-8. Epub 2010 Nov 17.

Abstract

Aim: This study aims to determine mechanisms of action of the gasotransmitter hydrogen sulfide (H(2)S) on contractile activity in longitudinal muscle of rat ileum.

Methods: Ileal longitudinal muscle strips were prepared to measure isometric contractions. Effects of sodium hydrosulfide (NaHS), a donor of H(2)S, were evaluated on spontaneous contractile activity and after enhanced contractile activity with bethanechol. L-cysteine was evaluated as a potential endogenous donor of H(2)S. We evaluated involvement of extrinsic nerves, enteric nervous system, visceral afferent nerves, nitric oxide, and K(ATP)(+) channel and K(Ca)(+) channel activity on the action of H(2)S using non-adrenergic/non-cholinergic conditions, tetrodotoxin, capsaicin, L-N(G)-nitro arginine (L-NNA), glibenclamide, and apamin, respectively, as well as electrical field stimulation.

Result: NaHS dose-dependently and reversibly inhibited spontaneous and bethanechol-stimulated contractile activity (p < 0.05). L-cysteine had no inhibitory effect. Non-adrenergic/non-cholinergic conditions, tetrodotoxin, capsaicin, L-NNA, glibenclamide, or apamin had no major effect on total contractile activity by NaHS, although both tetrodotoxin and apamin decreased the frequency of bethanechol-enhanced contractile activity (p < 0.05). We could not demonstrate H(2)S release by electrical field stimulation but did show that inhibition of cystathionine β synthase, an endogenous source of H(2)S, augmented the inhibitory effect of low-frequency electrical field stimulation.

Conclusion: H(2)S inhibits contractile activity of ileal longitudinal muscle dose-dependently but not through pathways mediated by the extrinsic or enteric nervous system, visceral afferent nerves, nitric oxide, K(ATP)(+) channels, or K(Ca)(+) channels.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Disease Models, Animal
  • Gastrointestinal Motility / drug effects*
  • Hydrogen Sulfide / pharmacology*
  • Ileum / drug effects
  • Ileum / physiology*
  • KATP Channels / drug effects
  • KATP Channels / metabolism
  • Male
  • Muscle Contraction / drug effects*
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology*
  • Rats
  • Rats, Inbred Lew

Substances

  • KATP Channels
  • Hydrogen Sulfide