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.