Previous studies based upon competition between different organic anions for biliary excretion in vivo have suggested that all organic anions share a common hepatic secretory mechanism. Corriedale sheep with an inherited defect in organic anion excretion by the liver were used to study this problem directly without the need for competition studies, the results of which are difficult to analyze. Maximal biliary excretion of sulfobromphthalein (BSP) in mutant Corriedale sheep was less than 7% of that observed in normal sheep whereas maximal biliary excretion of taurocholate, the major organic anion in sheep bile, was not different in mutant and normal sheep. Taurocholate infusion enhanced maximal hepatic excretion of BSP in normal but not in mutant sheep. These studies of an inheritable disorder which appears to be identical to the Dubin-Johnson syndrome in man, demonstrate that taurocholate excretion requires at least one step in biliary excretion which is not required by other organic anions such as bile pigment, porphyrins, drugs, and dyes.The organic anions in m a m m a l i a n bile consist of bile acids, bile pigments, porphyrins, metabolites, dyes, and drugs which are believed to be excreted by the parenchymal liver cell (1-3) and which are present in bile in concentrations very much greater than their simultaneous concentrations in plasma (2). It has been proposed that the organic anions excreted in bile share a common secretory mechanism because of their similarity to the group of compounds secreted by the renal organic anion transport mechanism (4), although bile salts are actively reabsorbed by the kidney tubule whereas phenol red, another organic anion, is actively secreted (5). Parenteral administration of some organic anions depresses the biliary excretion of other organic anions when administered simultaneously (2). Demonstration of competition for biliary excretion in vivo between different organic anions is complicated because m a n y of these compounds may share common binding to serum proteins, mechanisms of entry into liver cells, and various intraceUular metabolic trans-238
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