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Am J Physiol Gastrointest Liver Physiol 253: G737-G744, 1987;
0193-1857/87 $5.00
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AJP - Gastrointestinal and Liver Physiology, Vol 253, Issue 6 737-G744, Copyright © 1987 by American Physiological Society


ARTICLES

Opiate activity and transepithelial passage of intact beta-casomorphins in rabbit ileum

D. Tome, A. M. Dumontier, M. Hautefeuille and J. F. Desjeux
Unite de Recherche, Institute National de la Sante et de la Recherche Medicale U.290, Hopital Saint-Lazare, Paris, France.

The functional significance of the presence of opioid peptides in enzymatic digestion of food proteins remains uncertain. The effect of natural beta-casomorphins (beta-CMs), beta-CM-5 and beta-CM-4-NH2 (morphiceptine), and the analogue beta-[D-Ala2,4,Tyr5]CM-5-NH2 were studied in isolated rabbit ileum mounted in Ussing chambers. All three peptides caused a naloxone-reversible reduction in short-circuit current (Isc) after addition at a concentration of 10(-4) M to the serosal side of the tissue. After addition to the mucosal side, only the analogue beta-[D-Ala2,4,Tyr5]CM-5-NH2 reduced Isc. Natural beta-CMs were degraded by the intestinal mucosa, and no intact transepithelial passage was detected for these peptides, whereas beta-[D-Ala2,4,Tyr5]CM-5-NH2 was demonstrated to cross the epithelium intact when added at a concentration of 10(-3) M in the mucosal reservoir (mucosal-to-serosal flux = 3.5 +/- 1.2 nmol.h-1.cm-2). These results show that both natural beta-CMs and the protected analogue have an opiate activity on intestinal electrolyte transport. Their action from the luminal side of the intestine seems to depend on the transfer of the intact peptides from the luminal to the blood side of the tissue where opiate receptors are located. This action is prevented by luminal hydrolysis of the natural peptides.


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