Myosin light chain phosphatase activation is involved in the hydrogen sulfide-induced relaxation in mouse gastric fundus.
The relaxant effect of hydrogen sulfide (H(2)S) in the vascular tree is well established but its influence and mechanism of action in gastrointestinal smooth muscle was hardly investigated. The influence of H(2)S on contractility in mouse gastric fundus was therefore examined. Sodium hydrogen sulfide (NaHS; H(2)S donor) was administered to prostaglandin F(2alpha) (PGF(2alpha))-contracted circular muscle strips of mouse gastric fundus, before and after incubation with interfering drugs. NaHS caused a concentration-dependent relaxation of the pre-contracted mouse gastric fundus strips. The K(+) channels blockers glibenclamide, apamin, charybdotoxin, 4-aminopyridin and barium chloride had no influence 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, ryanodine 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(2alpha)-contracted mouse gastric fundus strips. The results suggest that in the mouse gastric fundus, H(2)S causes relaxation at least partially via activation of MLCP.
Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium.
Ingeborg
I
Dhaese
Romain A
RA
Lefebvre
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000577:Amides / Q000494:pharmacology; D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D005748:Gastric Fundus / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D005905:Glyburide / Q000494:pharmacology; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008387:Marine Toxins; D051379:Mice; D009126:Muscle Relaxation / Q000187:drug effects*; D043263:Myosin-Light-Chain Phosphatase / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology; D020960:omega-Conotoxins / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D000577:Amides; D008387:Marine Toxins; D010080:Oxazoles; D011725:Pyridines; D020960:omega-Conotoxins; C108830:Y 27632; C017759:9-(tetrahydro-2-furyl)-adenine; D013779:Tetrodotoxin; C059041:calyculin A; D054460:rho-Associated Kinases; D043263:Myosin-Light-Chain Phosphatase; D020742:rhoA GTP-Binding Protein; D000225:Adenine; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester; D006862:Hydrogen Sulfide