beta-Endorphin and enkephalins stimulate duodenal mucosal alkaline secretion in the rat in vivo.

Secretion of HCO3- by duodenum just distal to the Brunner's glands area and devoid of pancreatic HCO3- was titrated in situ in anesthetized rats. Secretion increased significantly after intravenous injection of small amounts (10-20 ng/kg) of the opioid peptides beta-endorphin, methionine-enkephalin, and leucine-enkephalin. Maximum (approximately twofold) stimulation by beta-endorphin and leucine-enkephalin occurred at 20 ng/kg. Morphine (50 micrograms/kg) caused a similar stimulation and the mu-selective opiate antagonist naloxone prevented the stimulation by beta-endorphin and morphine. The synthetic analogue [D-Ala2,D-Leu5]-enkephalin (500 ng/kg), which is an agonist primarily at delta-opiate receptors, had no effect, further suggesting that the stimulation of duodenal HCO3- secretion is mediated by mu-receptors. Naloxone alone did not affect basal HCO3- secretion but reduced the duration of the rise in secretion in response to a 5-min exposure to luminal acid (pH 2.00). Endogenous opioid peptides may thus have a role in the humoral or neural control, or both, of duodenal surface epithelial HCO3- secretion and mucosal protection.