Abstract

The opioid antagonist naloxone added after contractions induced by excitatory peptides on the myenteric plexus-longitudinal muscle preparation of the guinea pig ileum evoked a contracture with intensity dependent on the concentration of the antagonist and on the interval of time that elapsed after the cessation of the excitation induced by the peptides. A direct relationship was found between the component of the peptide-induced contraction that appeared to be neurally mediated and the magnitude of the subsequent contracture induced by naloxone. Moreover, the opioid agonist FK 33-824 decreased the contractile effect of the excitatory peptides and also increased the height of the naloxone-induced contractures. That effect was particularly evident when the higher doses of the peptides were studied. In the presence of atropine naloxone elicited small contractures when added after peptides with primarily neural actions, including corticotropin-releasing factor, neurotensin and cholecystokinin octapeptide 26-33 sulfated form. The naloxone-induced contracture appears to be mediated mainly by the release of acetylcholine, and to a minor extent by another spasmogenic substance from the myenteric plexus. It is concluded that endogenous opioids modulate, i.e., inhibit the release of those excitatory endogenous transmitters triggered by the effect of excitatory peptides upon the myenteric plexus.