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^-6M carbachol by exerting a direct action on muscle cells. In addition, the inhibitory effect of 2´,5´-dideoxy-adenosine (an inhibitor of adenylate cyclase), phorbol 12-myristate 13-acetate (an inhibitor of particulate guanylate cyclase), 6-anilinoquinoline-5,8-quinone (an inhibitor of soluble guanylate cyclase) and Nω-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 contractile response produced by 10^-6M 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 Nω-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.