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.