REVERSIBILITY OF ORGANIC ANION-INDUCED CHOLESTASIS - ASSOCIATION WITHCOMPENSATORY HYPERSECRETION OF BILIARY PHOSPHOLIPID AND PROTEIN IN THE DOG

The effect of a concomitant infusion of organic anions, structurally r elated phthaleins, on bile flow was studied in anaesthetized dogs. A c ombination of rose bengal and sulfobromophthalein was found to uniquel y and synergistically produce an acute, reversible form of intrahepati c cholestasis (< 100% of control level). This phenomenon was not obser ved with the administration of those individual organic anions at conc entrations previously associated with the induction of intrahepatic ch olestasis. The infusion of either a micelle forming bile salt, sodium taurocholate, or a non-micelle forming bile salt, sodium dehydrocholat e, rapidly reversed the intrahepatic cholestasis (within 20 min after bile salt infusion). During the choleretic phase immediately following the bile salt infusion, a transient but marked hypersecretion, a disp roportionately increased output in relation to that of bile acids, of biliary phospholipid (176% of control level by taurocholate and 138% o f control level by dehydrocholate), and an even more striking amount o f biliary protein hypersecretion were observed (392% of control level by taurocholate and 357% of control level by dehydrocholate). Although the significance of these new post-cholestatic observations requires clarification, it is suggested that the intrahepatic cholestasis induc ed by organic anions reflects a reversible defect in the mechanism(s) involved in transcellular transport.