Multidrug resistance P-glycoprotein 2 is essential for the biliary excretion of indocyanine green

Multidrug resistance P-glycoprotein 2 (Mdr2) is a phospholipid translocator in the canalicular membrane that is essential for the formation of biliary phospholipid vesicles and mixed lipid/bile salt micelles. Incorporation in to biliary vesicles and micelles is thought to contribute to the hepatobili ary excretion of certain hydrophobic organic anions, such as indocyanine gr een (ICG). The present studies characterized the biliary excretion of two h ydrophobic organic anions, ICG and estradiol-17 beta(beta -D-glucuronide) ( E(2)17G), in the single-pass isolated perfused liver and the biliary excret ion of glutathione (GSH) in vivo in wild-type and Mdr2(-/-) female mice. Th e biliary excretion of ICG (0.4 mu mol) was reduced by 90%, while the bilia ry excretion of total GSH was decreased by 65% in Mdr2(-/-) mice relative t o wild-type mice. In contrast, the biliary excretion of E(2)17G (0.1 mu mol ) was increased by 30% in Mdr2(-/-) mice. These data indicate that the abse nce of Mdr2 differentially influences the biliary excretion of these organi c anions and suggest that phospholipid vesicles and mixed micelles in bile are essential for the biliary excretion of ICG.