MECHANISM OF BILE-ACID FACILITATION OF BILIARY PROTOPORPHYRIN EXCRETION IN RAT-LIVER

The mechanism(s) by which bile acids increase biliary protoporphyrin e xcretion was characterized using perfused rat livers. We determined 1) relationships between biliary bile acids, phospholipid, and protoporp hyrin, using rapid kinetic analyses; 2) protoporphyrin excretion in li vers with defective canalicular multispecific organic anion transport; 3) effects of intracellular vesicular transport inhibition with colch icine and monensin; and 4) the role of luminal bile acids, using retro grade intrabiliary taurocholate injections. Biliary protoporphyrin exc retion peaked with phospholipid excretion 14-18 min after loading. Pro toporphyrin excretion induced by taurocholate was not related to effec ts on intracellular transport, including colchicine- and monensin-inhi bitable vesicular systems. Eisai hyperbilirubinemic rat livers excrete d protoporphyrin similarly to controls. Retrograde intrabiliary tauroc holate injections increased protoporphyrin phyrin output. Collectively , these data suggest that 1) intracellular protoporphyrin transport is mediated by nonvesicular carriers targeted to the canalicular membran e, and 2) bile acid facilitates protoporphyrin translocation into bile in the same manner it effects phospholipid excretion.