INVOLVEMENT OF NITRIC-OXIDE IN THE SUBSTANCE-P-INDUCED INHIBITION OF INTESTINAL PERISTALSIS

ALTHOUGH considered as an intestinal motor stimulant, substance P can inhibit intestinal peristalsis via stimulation of tachykinin NK1 recep tors. Since NK1 receptors are present on enteric nitrergic neurones, t he contribution of nitric oxide (NO) to the peristaltic motor inhibiti on caused by tachykinins was examined in luminally perfused segments o f isolated guinea-pig ileum. Substance P (100 nM) and the NK1 receptor agonist substance P methyl ester (100 nM) increased the intraluminal pressure threshold at which peristaltic contractions were elicited. Th is inhibitory influence on peristalsis was prevented by the NO synthas e inhibitor N-G-nitro-L-arginine methyl ester (300 mu M) in an enantio mer-selective manner. It is concluded that the substance P/NK1 recepto r-mediated depression of intestinal peristalsis involves inhibitory mo tor pathways utilizing NO as a transmitter.