Xenobiotics Inhibit Hepatic Uptake and Biliary Excretion of Taurocholate in Rat Hepatocytes

Reports suggest that troglitazone, and to a lesser extent bosentan, may alter bile acid homeostasis by inhibiting the bile salt export pump.Thepresent studies examined the hypothesis that these xeno-biotics may modulate multiple hepatic bile acid transport mechan-isms. In suspended rat hepatocytes, troglitazone (10 mM) decreased the initial rate of taurocholateuptake3-fold; the initial uptake rate of estradiol-17b-D-glucuronide, a substrate of the organic anion transporting polypeptides, also was decreased 4-fold. Bosentan (100 mM) decreased the initial uptake rate of taurocholate and estradiol-17b-D-glucuronide by 12- and 7-fold, respectively. In sandwich-cultured rat hepatocytes, 10-min accumulation of taur-ocholate in cells 1 bile canaliculi (408 6 57 pmol/mg protein) was decreased significantly by troglitazone (1576 17 pmol/mg protein, respectively) only in the presence of Na1, the driving force for the sodiumtaurocholate cotransportingpolypeptide.A similardecreas