MET-ENKEPHALIN-DEPENDENT NITRERGICALLY MEDIATED RELAXATION IN THE GUINEA-PIG ILEUM

Met-enkephalin-induced modulation of tetrodotoxin (0.1 mu M)-sensitive nonadrenergic, noncholinergic (NANC) nerve-mediated responses of the longitudinal muscle layer of guinea pig ileum during electrical field stimulation (EFS, 0.8 ms, 40 V, 20 s, 1 Hz or 10 Hz) were studied. The response to EFS of untreated preparations was a twitch followed by a low-amplitude tonic contraction. The NANC nerve-mediated response reve aled in the presence of phentolamine (5 mu M), propranolol (5 mu M) an d atropine (3 mu M) consisted of relaxation followed by a twitch and a tonic contraction. The relaxation was inhibited by N-G-nitro-L-argini ne (0.1-0.5 mM), a nitric oxide synthase inhibitor: L-arginine (0.5 mM ), a substrate of nitric oxide synthase, restored the relaxation to th e initial level indicating its nitrergic origin. After adenosine 5'-tr iphosphate-induced desensitization of purinoceptors the relaxation was enhanced while the contractions decreased Met-enkephalin (1 nM-1 mu M ) abolished (1-Hz EFS) or reduced (10-Hz EFS) the relaxation in a freq uency-dependent manner, suggesting an inhibitory prejunctional enkepha linergic mechanism modulating the nitrergically mediated relaxant even ts in the longitudinal muscle layer.