Enkephalin inhibits the release and action of secretin on pancreatic secretion in the dog.

1. Pancreatic bicarbonate and protein secretion as well as immuno-reactive plasma secretin concentration in response to a meal, duodenal acidification and exogenous secretin or octapeptide of cholecystokinin (OP-CCK) have been measured following administration of methionine-enkephalin in chronic pancreatic fistula dogs. 2. Methionine-enkephalin inhibited pancreatic responses to both exogenous hormones (secretin and OP-CCK) and to endogenous hormones released from the gut by food or duodenal acidification. 3. Naloxone, a potent opiate receptor antagonist, partly prevents this methionine-enkephalin-induced inhibition of pancreatic secretion suggesting that this effect might be mediated by opiate receptors. 4. The inhibitory effect of methionine-enkephalin on pancreatic response to endogenous stimulants was more pronounced than that to exogenous hormones and was accompanied by a significant reduction in plasma immuno-reactive secretin concentration. 5. This study indicates that methionine-enkephalin inhibits pancreatic secretion, at least in part, by suppressing the release of the intestinal hormones stimulating the exocrine pancreas.