Dual effect of exogenous hydrogen sulfide on the spontaneous contraction of gastric smooth muscle in guinea-pig

Eur J Pharmacol. 2009 Aug 15;616(1-3):223-8. doi: 10.1016/j.ejphar.2009.05.014. Epub 2009 May 23.

Abstract

Hydrogen sulfide (H(2)S) is produced endogenously in mammalian tissues and is important in both physiological and pathological processes. Despite its importance, little is known regarding the effect of H(2)S on gastrointestinal motility. We evaluated the effect of H(2)S on the spontaneous contraction of gastric antrum smooth muscle in the guinea pig (Cavia porcellus) using a physiograph. In addition, we investigated whether the effect of H(2)S was mediated by ionic channels by recording membrane currents in freshly dispersed gastric antrum myocytes using a whole-cell patch clamp. Sodium hydrogen sulfide (NaHS), an H(2)S donor, had a dual effect on the spontaneous contraction of gastric antrum muscle strips. At high concentrations (0.3-1.0 mM), NaHS suppressed the amplitude of spontaneous contraction. At low concentrations (0.1-0.3 mM), NaHS enhanced the resting tension of muscle strips while slightly reducing the contractile amplitude. The excitatory effect on spontaneous contraction, caused by low concentrations of NaHS, was abolished when the muscle strips were pretreated with 10 mM tetraethylammonium (TEA), a nonselective potassium channel blocker, or 0.5 mM 4-Aminopyridine (4-AP), a voltage-gated K(+) channel blocker. However, the excitatory effect of NaHS was not completely blocked by low concentrations of TEA (1 mM). Pretreatment with both TEA (1 mM) and 4-AP (0.5 mM) completely abolished the excitatory effect. The dose-response curve for the inhibitory effect of NaHS on the spontaneous contraction of gastric smooth muscle was shifted significantly to the left by TEA and 4-AP. Both Pinacidil, a K(ATP) channel opener, and NaHS significantly inhibited TEA-potentiated spontaneous contraction. Glibenclamide, a K(ATP) channel blocker, partially, but significantly, reversed the reduction in amplitude. NaHS enhanced the amplitude of the K(ATP) current, but inhibited the voltage-gated K(+) channel current (IK(V)) in a dose-dependent manner. NaHS had no effect on STOC at low concentrations (0.1-1.0 mM) but significantly inhibited STOC at high concentrations (4-10 mM). Our results suggest that H(2)S has multiple actions during the regulation of gastric motility in the guinea-pig. An excitatory effect is mediated via inhibition of the voltage-gated K(+) channel and an inhibitory effect is mediated via activation of the K(ATP) channel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Electric Conductivity
  • Female
  • Guinea Pigs
  • Hydrogen Sulfide / pharmacology*
  • In Vitro Techniques
  • Male
  • Muscle Contraction / drug effects*
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / metabolism
  • Muscle, Smooth / physiology*
  • Potassium Channels / metabolism
  • Pyloric Antrum*
  • Sulfides / pharmacology

Substances

  • Potassium Channels
  • Sulfides
  • sodium bisulfide
  • Hydrogen Sulfide