Myosin light chain phosphatase activation is involved in the hydrogen sulfide-induced relaxation in mouse gastric fundus

The relaxant effect of hydrogen sulfide (H2S) in the vascular tree is well established but its influence and mechanism of action in gastrointestinal smooth muscle was hardly investigated. The influence of H2S on contractility in mouse gastric fundus was therefore examined. Sodium hydrogen sulfide (NaHS; H2S donor) was administered to prostaglandin F-2 alpha (PGF(2 alpha))-contracted circular muscle strips of mouse gastric fundus, before and after incubation with interfering drugs. NaHS caused a concentration-depedent relaxation of the pre-contracted mouse gastric fundus strips. The K+ channels blockers glibenclamide, apamin, charybdotoxin, 4-aminopyridin and barium chloride had no influecne on the NaHS-induced relaxation. The relaxation by NaHS was also not influenced by L-NAME, ODQ and SQ 22536, inhibitors of the cGMP and CAMP pathway, by nerve blockers capsazepine, omega-conotoxin and tetrodotoxin or by several channel and receptor blockers (ouabain, nifedipine, 2-aminoethyl diphenylborinate, rynanodine and thapsigargin). The myosin light chain phosphatase (MLCP) inhibitor calyculin-A reduced the NaHS-induced relaxation, but the Rho-kinase inhibitor Y-27632 had no influence. We show that NaHS is able to relax PGF(2 alpha)-contracted mouse gastric fundus strips. The results suggest that in the mouse gastric fundus, H2S causes relaxation at least partially via activation of MLCP. (C) 2009 Elsevier B.V. All rights reserved.