Milk Bioactive Peptides and β-Casomorphins Induce Mucus Release in Rat Jejunum

Abstract

Intestinal mucus is critically involved in the protection of the mucosa. An enzymatic casein hydrolysate and β-casomorphin-7, a μ-opioid peptide generated in the intestine during bovine casein digestion, markedly induce mucus discharge. Because shorter μ-opioid peptides have been described, the effects of the opioid peptides in casein, β-casomorphin-7, -6, -4, -4NH2 and -3, and of opioid neuropeptides met-enkephalin, dynorphin A and (D-Ala2,N-Me-Phe4,glycinol5)enkephalin (DAMGO) on intestinal mucus secretion were investigated. The experiments were conducted with isolated perfused rat jejunum. Mucus secretion under the influence of β-casomorphins and opioid neuropeptides administered intraluminally or intra-arterially was evaluated using an ELISA for rat intestinal mucus. Luminal administration of β-casomorphin-7 (1.2 × 10-4 mol/L) provoked a mucus discharge (500% of controls) that was inhibited by naloxone, a specific opiate receptor antagonist. Luminal β-casomorphin-6, -4 and -4NH2 did not modify basal mucus secretion, whereas intra-arterial administration of β-casomorphin-4 (1.2 × 10-6 mol/L) induced a mucus discharge. In contrast, intra-arterial administration of the nonopioid peptide β-casomorphin-3 did not release mucus. Among the opioid neuropeptides, intra-arterial infusion of Met-enkephalin or dynorphin-A did not provoke mucus secretion. In contrast, β-endorphin (1.2 × 10 -8 to 1.2 × 10-6 mol/L) induced a dose-dependent release of mucus (maximal response at 500% of controls), DAMGO (1.2 × 10-6 mol/L), a μ-receptor agonist, also evoked a potent mucus discharge. Our findings suggest that μ-opioid neuropeptides, as well as β-casomorphins after absorption, modulate intestinal mucus discharge. Milk opioid-derived peptides may thus be involved in defense against noxious agents and could have dietary and health applications.