[Biliary transport of organic anions in the isolated hemoglobin-free perfused rat liver (author's transl)].
Mechanisms involved in the biliary excretion of organic anions were investigated in hemoglobin-free perfused rat liver using iotroxic acid as a test substance. The process of biliary excretion in this system can be separated into three elemental processes, i.e. 1) diffusion into hepatocytes, 2) protein-binding with intracellular protein (accumulation) and 3) active transport into bile. Elimination of iotroxic acid from the perfusate into the hepatocytes followed first-order kinetics, indicating the process to be that of passive diffusion. Though the biliary excretion occurred rather rapidly, the amount of iotroxic acid in the hepatocytes increased with increases in the initial concentration in the perfusate and approached a maximal amount of ca. 2.8 mu moles/g wet weight of liver. The maximal values observed for the biliary concentration and the rate of biliary transport were 20-24 mM and 38-48 nmoles/min . g liver, respectively. Bromsulphalein inhibited the diffusion of iotroxic acid into the hepatocytes whereas accumulation of iopodic acid in the hepatocytes produced an inhibition of diffusion into the hepatocytes and transport into the bile. Dexamethasone-21-sulfate (DXMS) was transported rapidly into the bile, but in the presence of iotroxic or iopodic acids, excretion of DXMS into the bile was inhibited, while diffusion into the hepatocytes was inhibited only by iopodic acid. The competition observed with those substances demonstrates the presence of a common mechanism for the biliary transport of organic anions in the liver.
D000818:Animals; D000838:Anions; D001646:Bile / Q000378:metabolism*; D001667:Binding, Competitive; D001693:Biological Transport, Active; D003907:Dexamethasone / Q000378:metabolism; D004347:Drug Interactions; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D010477:Perfusion; D011485:Protein Binding; D051381:Rats; D013448:Sulfobromophthalein / Q000378:metabolism; D014283:Triiodobenzoic Acids / Q000378:metabolism
D000838:Anions; D014283:Triiodobenzoic Acids; D013448:Sulfobromophthalein; D003907:Dexamethasone