Choleresis and hepatic transport mechanisms. II. Influence of bile salt choleresis and biliary micelle binding on biliary excretion of various organic anions.
To investigate, whether binding to micelles has a function in hepatic transport, biliary excretion of three organic anions, phenolphthalein-beta-D-glucuronide (PG), dibromosulphthalein (DBSP) and indocyanine green (ICG) was studied in rats during saline, taurocholate or dehydrocholate administration. Taurocholate causes a weak choleresis with formation of biliary micelles, dehydrocholate a strong choleresis with little micelle formation. The two bile salts did not uniformly influence biliary excretion of the organic anions: biliary excretion of ICG (12.9 mumoles/kg) and DBSP (75.0 mumoles/kg) was stimulated by both bile salts: ICG excretion most pronounced by taurocholate and DBSP excretion most strongly by dehydrocholate. Biliary output of PG (25.8 and 200 mumoles/kg) was not stimulated by bile salt administration. Binding of PG, DBSP and ICG to biliary micelles was studied in sedimentation experiments by ultracentrifugation. PG, DBSP and ICG in bile showed a similar sedimentation pattern as 3H-taurocholate in bile, which indicates an association of all three anions with biliary micelles. Thus, the influence of bile salts on biliary transport of organic anions varies with the compound studied and the bile salt used, effects which cannot be explained by differences in binding to biliary micelles.
D000818:Animals; D001646:Bile / Q000378:metabolism*; D001647:Bile Acids and Salts / Q000494:pharmacology*; D001665:Binding Sites; D001692:Biological Transport / Q000187:drug effects; D003685:Dehydrocholic Acid / Q000494:pharmacology; D005965:Glucuronates / Q000378:metabolism; D007208:Indocyanine Green / Q000378:metabolism; D008297:Male; D008823:Micelles / Q000378:metabolism; D010635:Phenolphthaleins / Q000378:metabolism; D051381:Rats; D013448:Sulfobromophthalein / Q000378:metabolism; D013656:Taurocholic Acid / Q000494:pharmacology
D001647:Bile Acids and Salts; D005965:Glucuronates; D008823:Micelles; D010635:Phenolphthaleins; D013448:Sulfobromophthalein; D013656:Taurocholic Acid; D007208:Indocyanine Green; D003685:Dehydrocholic Acid