Met-enkephalin-dependent nitrergically mediated relaxation in the guinea pig ileum.

Met-enkephalin-induced modulation of tetrodotoxin (0.1 microM)-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 revealed in the presence of phentolamine (5 microM), propranolol (5 microM) and atropine (3 microM) consisted of relaxation followed by a twitch and a tonic contraction. The relaxation was inhibited by NG-nitro-L-arginine (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 the initial level indicating its nitrergic origin. After adenosine 5'-triphosphate-induced desensitization of purinoceptors the relaxation was enhanced while the contractions decreased. Met-enkephalin (1 nM-1 microM) abolished (J-Hz EFS) or reduced (10-Hz EFS) the relaxation in a frequency-dependent manner, suggesting an inhibitory prejunctional enkephalinergic mechanism modulating the nitrergically mediated relaxant events in the longitudinal muscle layer.