Excitatory neuropeptides activate opioid mechanisms in the guinea pig ileum.

A variety of peptides (corticotropin releasing factor (= CRF), cholecystokinin-derived peptides, neurotensin, bombesin, angiotensin II, bradykinin and substance P) induce a contraction of the myenteric plexus/longitudinal muscle preparation of the guinea-pig ileum. This excitatory effect is rapid in onset and disappears within a few minutes in the continued presence of the peptide. A part of the contractile response is antagonized by atropine indicating that acetylcholine (ACh) is involved in this effect. Following cessation of the peptide-induced contraction, a second contractile response can be elicited by the opioid antagonist naloxone. The magnitude of this naloxone induced contraction is related to the "atropine-sensitive" component of the initial contractory effect of the peptides. It appears that the peptidergic excitatory action on the plexus which is associated with release of ACh, initiates the release of opioid peptides in this tissue.