Cholecystokinin octapeptide activates an opioid mechanism in the guinea-pig ileum: a possible role for substance P.

To test the hypothesis that excitatory peptides release endogenous opioids from the myenteric plexus longitudinal muscle (MPLM) preparation of the guinea-pig ileum (GPI), the effect of cholecystokinin (CCK8) was studied in the absence and presence of the opioid antagonist naloxone. The maximum height of the contracture induced by CCK8 was not altered by the presence of naloxone in the incubation medium, however, the subsequent sustained excitation was clearly increased. This effect is interpreted as being a result of the release of endogenous opioids during the first moments of the CCK8-evoked excitation of the plexus. CCK8 still induced neurogenic contractures in the presence of atropine; these contractures were probably mediated by the release of substance P. Naloxone was used to evidence the opioid control of the CCK8-induced release of substance P. Desensitization to the effect of substance P reduced the action of CCK8 and also abolished the non-cholinergic contractures evoked by CCK8 and the subsequent effect of naloxone. These facts suggest the release of endogenous opioids within the plexus in response to the neurally mediated excitatory action of CCK8.