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Nutrient Metabolism

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

Aurélien Trompette^*, Jean Claustre^*, Fabienne Caillon^*, Gérard Jourdan^*, Jean Alain Chayvialle^* and Pascale Plaisancié^*,,1

^* INSERM U45, Faculté de médecine Laënnec, 7 rue G Paradin 69372 Lyon cedex 08, France and Laboratoire d’Ecologie et de Physiologie du Système Digestif, INRA, Centre de Recherche de Jouy-en-Josas, 78352 Jouy en Josas cedex, France

¹To whom correspondence should be addressed. E-mail: plaisancie{at}lyon.inserm.fr.

Intestinal mucus is critically involved in the protection of the mucosa. An enzymatic casein hydrolysate and ß-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, ß-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 ß-casomorphins and opioid neuropeptides administered intraluminally or intra-arterially was evaluated using an ELISA for rat intestinal mucus. Luminal administration of ß-casomorphin-7 (1.2 x 10^-4 mol/L) provoked a mucus discharge (500% of controls) that was inhibited by naloxone, a specific opiate receptor antagonist. Luminal ß-casomorphin-6, -4 and -4NH₂ did not modify basal mucus secretion, whereas intra-arterial administration of ß-casomorphin-4 (1.2 x 10^-6 mol/L) induced a mucus discharge. In contrast, intra-arterial administration of the nonopioid peptide ß-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, ß-endorphin (1.2 x 10^-8 to 1.2 x 10^-6 mol/L) induced a dose-dependent release of mucus (maximal response at 500% of controls). DAMGO (1.2 x 10^-6 mol/L), a µ-receptor agonist, also evoked a potent mucus discharge. Our findings suggest that µ-opioid neuropeptides, as well as ß-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.

KEY WORDS: • mucus • intestine • milk • casomorphin • opioid

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