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

Abstract

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 β-endorphin, methionine-enkephalin, and leucine-enkephalin. Maximum (~twofold) stimulation by β-endorphin and leucine-enkephalin occurred at 20 ng/kg. Morphine (50 μg/kg) caused a similar stimulation and the μ-selective opiate antagonist naloxone prevented the stimulation by β-endorphin and morphine. The synthetic analogue [d-Ala2,d-Leu5]-enkephalin (500 ng/kg), which is an agonist primarily at δ-opiate receptors, had no effect, further suggesting that the stimulation of duodenal HCO3− secretion is mediated by μ-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.