Milk bioactive peptides and beta-casomorphins induce mucus release in rat jejunum

J Nutr. 2003 Nov;133(11):3499-503. doi: 10.1093/jn/133.11.3499.


Intestinal mucus is critically involved in the protection of the mucosa. An enzymatic casein hydrolysate and beta-casomorphin-7, a mu-opioid peptide generated in the intestine during bovine casein digestion, markedly induce mucus discharge. Because shorter mu-opioid peptides have been described, the effects of the opioid peptides in casein, beta-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 beta-casomorphins and opioid neuropeptides administered intraluminally or intra-arterially was evaluated using an ELISA for rat intestinal mucus. Luminal administration of beta-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 beta-casomorphin-6, -4 and -4NH2 did not modify basal mucus secretion, whereas intra-arterial administration of beta-casomorphin-4 (1.2 x 10(-6) mol/L) induced a mucus discharge. In contrast, intra-arterial administration of the nonopioid peptide beta-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, beta-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 mu-receptor agonist, also evoked a potent mucus discharge. Our findings suggest that mu-opioid neuropeptides, as well as beta-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.

MeSH terms

  • Animals
  • Caseins / pharmacology
  • Endorphins / administration & dosage
  • Endorphins / pharmacology*
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / pharmacology
  • Infusions, Intra-Arterial
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism*
  • Jejunum
  • Male
  • Milk Proteins / pharmacology*
  • Mucus / metabolism*
  • Peptide Fragments / pharmacology
  • Rats
  • Rats, Wistar


  • Caseins
  • Endorphins
  • Milk Proteins
  • Peptide Fragments
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • beta-casomorphins