PARTIAL CHARACTERIZATION OF MECHANISM(S) BY WHICH SULPHOBROMOPHTHALEIN REDUCES BILIARY LIPID SECRETION

This study was performed to explore the mechanisms by which sulphobrom ophthalein (BSP) reduces the secretion of biliary lipid using Sprague- Dawley rats (SDR) and mutant rats with congenital conjugated hyperbili rubinaemia bred from SDR (EHBR). We infused the bile-salt-pool-deplete d rats with sodium taurocholate at a constant rate of 160 nmol/min per 100 g body wt. with BSP (12.5, 25 and 50 nmol/min per 100 g body wt.) or BSP-GSH (12.5, 25 and 50 nmol/min per 100 g body wt.). The biliary secretion of BSP and BSP-GSH was markedly impaired in EHBR as compare d with that in SDR. BSP reduced the biliary secretion of cholesterol a nd phospholipids in a dose-dependent manner without affecting the secr etion of bile salts and composition of fatty acids in phospholipids in SDR, but had no effect on lipid secretion in EHBR. In contrast, BSP-G SH had no such effect on biliary lipids, either in the SDR or EHBR. In addition, the amount of BSP in the liver of EHBR was in the same rang e as that of SDR. Therefore it is unlikely that an intracellular mecha nism is involved in the phenomenon of uncoupling by BSP. We conclude t hat the uncoupling of biliary lipids from bile-salt secretion by BSP o ccurs at the level of the bile canaliculus following the secretion of unconjugated BSP.