title: Direct inhibitory effect of thyrotropin-releasing hormone on isolated cecal circular smooth muscle cells of guinea pig.
abstract: Smooth muscle cells isolated from cecal circular smooth muscle of the guinea pig were used to determine whether thyrotropin-releasing hormone (TRH) can inhibit the contractile response produced by 10(-6) M carbachol by exerting a direct action on muscle cells. In addition, the inhibitory effect of 2',5'-dideoxyadenosine (an inhibitor of adenylate cyclase), phorbol 12-myristate 13-acetate (an inhibitor of particulate guanylate cyclase), 6-anilinoquinoline-5,8-quinone (an inhibitor of nitric oxide synthase) on the TRH-induced relaxation of cecal circular smooth muscle cells was examined. TRH inhibited the contractile response produced by 10(-6) M carbachol in a concentration-dependent manner, with an IC50 value of 4 nM, 2',5'-Dideoxyadenosine and phorbol 12-myristate 13-acetate did not have any significant effect on the TRH-induced relaxation. On the other hand, 6-anilinoquinoline-5,8-quinone and N omega-nitro-L-arginine methyl ester significantly inhibited the relaxation produced by TRH. Our findings show that TRH has a direct inhibitory effect on the isolated cecal circular smooth muscle cells via activation of nitric oxide synthase and soluble guanylate cyclase.
authors.affiliation: Third Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Harada
authors.forename: Y
authors.initials: Y
authors.lastname: Chijiiwa
authors.forename: H
authors.initials: H
authors.lastname: Akiho
authors.forename: H
authors.initials: H
authors.lastname: Okabe
authors.forename: H
authors.initials: H
authors.lastname: Nawata
mesh_terms: D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002432:Cecum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D048429:Cell Size / Q000187:drug effects; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000378:metabolism; D006152:Cyclic GMP / Q000037:antagonists & inhibitors / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*
chemical_list: D000634:Aminoquinolines; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D013973:Thyrotropin-Releasing Hormone; D002217:Carbachol; C041715:6-anilino-5,8-quinolinedione; D001120:Arginine; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D013755:Tetradecanoylphorbol Acetate; D019331:NG-Nitroarginine Methyl Ester