Transhepatic transport of taurocholic acid in normal and mutant analbuminemic rats.
To elucidate a possible function of plasma albumin in vectorial transport of various cholephilic organic anions, such as bile acids, plasma clearance and transhepatic transport of radioactive taurocholate were studied in vivo in normal and mutant analbuminemic rats. Intravenous administration of taurocholate was followed by its rapid disappearance from the circulation in both animal groups. However, plasma clearance of taurocholate was significantly larger in analbuminemic (68.3 ml/min per kg of body weight) than in normal rats (29.8 ml/min per kg of body weight) at a dose of 8 mumol/kg of body weight. The increased plasma clearance in analbuminemic rats was accompanied by a more prompt biliary secretion of the ligand than occurred in normal animals; 79 and 42% of the injected dose was recovered in analbuminemic and normal rat bile, respectively, within 10 min after administration. Ultrafiltration analysis revealed that the binding of taurocholate to serum protein(s) was significantly lower in analbuminemic rats as compared with that in normal rat serum; 24 and 76% of taurocholate bound to protein fractions of analbuminemic and normal rat serum, respectively, at 0.5-mM ligand concentration. Binding of taurocholate to cytosolic proteins of normal and analbuminemic liver were similar; 23 and 28% of taurocholate bound to protein fractions from analbuminemic and normal rat, respectively, at 10 mg protein/ml and 20-microM ligand concentration. These results indicate that plasma albumin does not play a role in directing circulating taurocholate to the liver and that transhepatic transport of the bile acid increases with the increase in concentration of unbound ligand in the circulation.
D000818:Animals; D001646:Bile / Q000378:metabolism; D001798:Blood Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins; D005982:Glutathione Transferase / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D051381:Rats; D011919:Rats, Inbred Strains; D012709:Serum Albumin / Q000172:deficiency*; D013656:Taurocholic Acid / Q000378:metabolism*
D001798:Blood Proteins; D002352:Carrier Proteins; D050556:Fatty Acid-Binding Proteins; D012709:Serum Albumin; D013656:Taurocholic Acid; D005982:Glutathione Transferase