HEPAIOCYTE MEMBRANE TRANSPORT MECHANISM OF VARIOUS SUBSTANCES

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(1)Canalicular membrane vesicles (CMV) of hepatocytes were prepared in pure form from the livers of normal SD rats and Eisai hyperbilirubinuric rats (HEBR). Mg^<++> -ATPase and alkaline phosphatase activities were highly enriched in the CMV.[ ^3H]Bilirubin diglucuronide (BDG) was purified from the hile of rats injected with [ ^3H]DELTA ALA.(2)Transport of [ ^3H]BDG and [ ^3H]taurocholate (TC) was observed using CMV from livers of SD rats and EHBR, and any differences of their transport between the 2 rat strains were compared. ATP-dependent [ ^3H]TC transport was present both in SD rat CMV and EHBR CMV.On the other hand, [ ^3H]BDG transport was not ATP-dependent and was increased in the presence of bicarbonate ion. This bicarbonate-dependent [ ^3H]BDG transport was also intact in EHBR CMV.(3)[^<14>C]Pravastatin (PS), One of model organic anions, is excreted in the bile of SD rats. However, its biliary excretion was found to be extremely delayd in EHBR.[^<14>C]PS transport by SD rat CMV was studied and found to be ATP-dependent. In contrast to the in vivo biliary excretion defect of PS, normal ATP-dependent PS transport was found in EHBR CMV.(4)From these results. the postulated defect in ATP-dependent organic anion transport in congenitally jaundiced EHBR was not confirmed and the presence of a novel ATP-dependent organic anion transporter was suugested on the canalicular membrane of rat hepatocytes.