DIRECT INHIBITORY EFFECT OF THYROTROPIN-RELEASING-HORMONE ON ISOLATEDCECAL CIRCULAR SMOOTH-MUSCLE CELLS OF GUINEA-PIG

Smooth muscle cells isolated from cecal circular smooth muscle of the guinea pig were used to determine whether thyrotropin-releasing hormon e (TRH) can inhibit the contractile response produced by 10(-6) M carb achol by exerting a direct action on muscle cells. In addition, the in hibitory effect of 2',5'-dideoxyadenosine (an inhibitor of adenylate c yclase), phorbol 12-myristate 13-acetate (an inhibitor of particulate guanylate cyclase), 6-anilinoquinoline-5,8-quinone (an inhibitor of so luble guanylate cyclase) and N omega-nitro-L-arginine methyl ester (an inhibitor of nitric oxide synthase) on the TRH-induced relaxation of cecal circular smooth muscle cells was examined. TRH inhibited the con tractile response produced by 10(-6) M carbachol in a concentration-de pendent manner, with an IC50 value of 4 nM. 2',5'-Dideoxyadenosine and phorbol 12-myristate 13-acetate did not have any significant effect o n the TRH-induced relaxation. On the other hand, 6-anilinoquinoline-5, 8-quinone and N omega-nitro-L-arginine methyl ester significantly inhi bited 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 c yclase.