In vitro effects of beta-casomorphins on ion transport in rabbit ileum.
beta-Casomorphins (beta-CM) represent opioid peptides derived from bovine beta-casein. As opiates are known to decrease short-circuit current (Isc) and stimulate intestinal electrolyte absorption, we tested the effects of natural beta-CM-4-OH, beta-CM-5-OH, and three related analogues on electrolyte transport in rabbit ileum in vitro. At concentrations of 10(-7) to 10(-3) M, the three analogues (beta-[D-Ala2]CM-4-NH2, beta-[D-Ala2,Met5]CM-5-NH2, and beta-[D-Ala2,4,Tyr5]CM-5-NH2) caused a dose-dependent, naloxone-reversible reduction in Isc after addition to the serosal side of the preparation. beta-[D-Ala2,4,Tyr5]CM-5-NH2 also decreased Isc after mucosal addition. Serosal addition of the same analogue stimulated absorption of sodium and chloride (+2.90 +/- 0.95 and +2.12 +/- 0.60 mu eq . h-1 . cm-2, respectively) and inhibited residual flux (-1.80 +/- 0.57 mu eq . h-1 . cm-2). The natural beta-CM tested did not decrease Isc. These results demonstrate that beta-CM analogues stimulate intestinal absorption of electrolytes by an opioid mechanism. The fact that beta-[D-Ala2,4,Tyr5]CM-5-NH2 was effective on the mucosal side favored the hypothesis that certain food-related opioid peptides might be absorbed by the intestine.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D004558:Electric Stimulation; D004723:Endorphins / Q000494:pharmacology*; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects*; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D007477:Ions / Q000378:metabolism*; D009270:Naloxone / Q000494:pharmacology; D011817:Rabbits; D012704:Serous Membrane / Q000187:drug effects
D004723:Endorphins; D007477:Ions; D009270:Naloxone; D004744:Enkephalin, Methionine; C013801:enkephalin-Met, Ala(2)-; C021968:beta-casomorphins