Amino acids are potent inhibitors of bile acid uptake by liver plasma membrane vesicles isolated from suckling rats.
We studied the effects of amino acids which undergo Na+-coupled cotransport on taurocholate uptake by basolateral liver plasma membrane vesicles prepared from 14-day-old rats. At concentrations similar to the total concentration of Na-dependent amino acids measured in portal blood, the Na+-dependent amino acids, L-alanine and L-glutamine, reduced the initial velocity of Na+-dependent taurocholate uptake and impaired uphill transport of the bile acid. In contrast, the Na+-independent amino acid, 2-aminobicyclo(2,2,1)heptane-2-carboxylic acid, did not affect taurocholate uptake. The inhibitory effect of Na+-dependent amino acids on taurocholate uptake was dose dependent. Taurocholate uptake was electroneutral and the inhibition of bile acid uptake by L-glutamine was not affected by the electrical potential. In the absence of a sodium gradient, but with equal intravesicular and extravesicular sodium concentrations, L-glutamine did not inhibit bile acid uptake. With an inwardly directed Na+ gradient, 22Na+ uptake (8 s) was 27% higher in the presence of L-glutamine (5 mM) than without L-glutamine. Kinetic analysis showed that L-glutamine (5 mM) decreased the maximum velocity of Na+-dependent taurocholate uptake to 59% of control (1.62 +/- 0.20 versus 2.73 +/- 0.30 nmol . mg-1 protein . min-1; p less than 0.002), but had no effect on the taurocholate Km (91.7 +/- 26.4 versus 97.1 +/- 25.4 microM). We conclude that physiologic concentrations of Na+-dependent amino acids markedly inhibit taurocholate uptake by membrane vesicles from 14-day rat livers.(ABSTRACT TRUNCATED AT 250 WORDS)
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D000833:Animals, Suckling; D001647:Bile Acids and Salts / Q000378:metabolism*; D001693:Biological Transport, Active / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism; D013656:Taurocholic Acid / Q000378:metabolism
D000596:Amino Acids; D001647:Bile Acids and Salts; D013656:Taurocholic Acid; D012964:Sodium