Mechanisms of action of hydrogen sulfide in relaxation of mouse distal colonic smooth muscle

Eur J Pharmacol. 2010 Feb 25;628(1-3):179-86. doi: 10.1016/j.ejphar.2009.11.024. Epub 2009 Nov 15.


Hydrogen sulfide (H(2)S) has been suggested as a gaseous neuromodulator in mammals. The aim of this study was to examine the influence of H(2)S on contractility in mouse distal colon. The effect of sodium hydrogen sulfide (NaHS; H(2)S donor) on prostaglandin F(2alpha) (PGF(2alpha))-contracted circular muscle strips of mouse distal colon was investigated. In addition, tension and cytosolic calcium concentration ([Ca(2+)](cyt)) in the mouse distal colon strips were measured simultaneously in the presence of NaHS. NaHS caused concentration-dependent relaxation of the pre-contracted mouse distal colon strips. The NaHS-induced relaxation was not influenced by the K(+) channels blockers glibenclamide, apamin, charybdotoxin, barium chloride and 4-aminopyridine. The relaxation by NaHS was also not influenced by the nitric oxide inhibitor L-NAME, by the soluble guanylate cyclase respectively adenylate cyclase inhibitors ODQ and SQ 22536, by the nerve blockers capsazepine, omega-conotoxin and tetrodotoxin or by several channel and receptor blockers (ouabain, nifedipine, 2-aminoethyl diphenylborinate, ryanodine and thapsigargin). The initiation of the NaHS-induced relaxation was accompanied by an increase in [Ca(2+)](cyt), but once the relaxation was maximal and sustained, no change in [Ca(2+)](cyt) was measured. This calcium desensitization is not related to the best known calcium desensitizing mechanism as the myosin light chain phosphatase (MLCP) inhibitor calyculin-A and the Rho-kinase inhibitor Y-27632 had no influence. We conclude that NaHS caused concentration-dependent relaxations in mouse distal colon not involving the major known K(+) channels and without a change in [Ca(2+)](cyt). This calcium desensitization is not related to inhibition of Rho-kinase or activation of MLCP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium / metabolism
  • Colon / cytology*
  • Cytosol / drug effects
  • Cytosol / metabolism
  • Enzyme Inhibitors / pharmacology
  • Hydrogen Sulfide / pharmacology*
  • In Vitro Techniques
  • Male
  • Mice
  • Muscle Contraction / drug effects
  • Muscle Relaxation / drug effects*
  • Muscle, Smooth / cytology
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / metabolism
  • Muscle, Smooth / physiology*
  • Nervous System / drug effects
  • Potassium Channel Blockers / pharmacology
  • Potassium Channels / metabolism


  • Enzyme Inhibitors
  • Potassium Channel Blockers
  • Potassium Channels
  • Calcium
  • Hydrogen Sulfide