UNCOUPLING OF BILIARY LIP ID SECRETION FROM BILE ACID SECRETION BY ORGANIC ANIONS, DUE TO INTRACANALICULAR INTERACTION WITH BILE ACIDS

摘要

Biliary secretion of phospholipids (PL) and cholesterol (CH) is regulated by bile acids (BA). However, a number of organic anions (OA) has been shown to inhibit PL and CH secretion without affecting that of BA. The mechanism of this OA-effect is unclear. We studied this uncoupling phenomenon with 3 different OA in normal Wistar (NW) rats and Groningen Yellow (GY) Wistar rats. The GY strain has a genetic defect in biliary secretions of various OA (JCI 81: 1593-9, 1988). NW and GY rats with 8-day bile diversion were injected intravenously with ampicillin (18 mol.100 g BW), sufated taurolithocholic acid (STLC, 1.0 umol/100gBW) or idocyanine green (ICG, 0.6 umol/100g BW). At 1 hr after injection recoveries in bile were: ampicillin, 4.1% and 0.5%; STLC 98% and 32%; ICG, 39% and 9%, in NW and GY rats, respectively. Ampicillin and STLC caused a strong uncoupling in NW rats (maximal BA.(PL+CH) -ratio+ 70% (ampicillin) and +147%(STLC), but no (ampicillin) or a much smaller (STLC +65%) uncoupling in GY rats. ICG injections did not induce an uncoupling, either in NW rats or in GY rats. The hetatic uptake of the used OA appeared to be unaffected in GY rats. Gel filtration chromatography (Sepharose CL-4B) showed that ampicillin and STLC coeluted with BA, while ICG coeluted with the PL and CH fraction. We conclude that the uncoupling of biliary PL and CH from BA secretion by ampicillin and STLC is not due to disturbance of processes at intracellular or bile canalicular membrane level, but to interactions with BA inside the canalicular lumen which disturb PL and CH solubilization.