The inhibitory effect of substance P on gastric motor function in the nucleus raphe obscurus is mediated via nitric oxide in the dorsal vagal complex

Abstract

We have previously shown that substance P (SP), microinjected into the caudal nucleus raphe obscurus (nROb) of the rat decreases intragastric pressure via a vagally mediated pathway. Recent studies from this laboratory demonstrated that nitric oxide (NO) synthase is present in the dorsal vagal complex (DVC) and NO synthase blockade in the DVC of the rat with N G-nitro- l-arginine methyl ester ( l-NAME) evokes increases in intragastric pressure. Since the nROb controls gastric vagal outflow through the DVC, we tested the hypothesis that NO in the DVC is a mediator of inhibitory effects of SP on gastric motor function in the nROb. Substance P (135 pmol) was microinjected into the nROb 3–6 min after bilateral microinjections of l-NAME (45 nmol per site) into the DVC of chloraloseanesthetized rats were started. Changes in the area of the response for intragastric pressure on microinjection of SP after l-NAME did not differ from the effect of vehicle microinjected after l-NAME and were significantly lower when compared with the effect of SP microinjected after vehicle. We conclude that SP in the nROb releases NO in the DVC to mediate the inhibitory effect on intragastric pressure.