NEURONAL PATHWAY INVOLVED IN NITRIC OXIDE-MEDIATED DESCENDING RELAXATION IN RAT ILEUM

The neuronal pathway that initiates nitric oxide-mediated descending r elaxation in rat ileum was studied. The descending relaxation, which w as suggested to be mediated by nitric oxide from our previous study, w as selectively inhibited by 5-HT3 receptor antagonists. It was also in hibited by a nicotinic acetylcholine receptor antagonist. Exogenous 5- hydroxytryptamine (5-HT) and a selective 5-HT3 receptor agonist induce d dose-dependent relaxation of ileal circular muscle. 5-HT-induced rel axation was selectively inhibited by 5-HT3 receptor antagonists. Nicot ine also induced relaxation of the circular muscle, and its effect was inhibited by 5-HT3 receptor antagonists. 5-HT and nicotine increased the cyclic GMP content of the ileal tissue. Nitro-L-arginine inhibited the increases induced by both compounds in the cyclic GMP content, an d a 5-HT3 receptor antagonist also inhibited that induced by nicotine. These results indicate that activation of a cholinergic neuron-5-HT n euron pathway initiates nitric oxide-mediated descending relaxation in rat ileum.