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Vol. 29, Issue 5, 634-637, May 2001
Graduate Center for Toxicology, 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 into biliary vesicles and micelles is thought
to contribute to the hepatobiliary excretion of certain hydrophobic
organic anions, such as indocyanine green (ICG). The present studies
characterized the biliary excretion of two hydrophobic organic anions,
ICG and estradiol-17
University of Kentucky,
Lexington, Kentucky
(-D-glucuronide)
(E217G), in the single-pass isolated perfused liver and the
biliary excretion of glutathione (GSH) in vivo in wild-type and
Mdr2
/ female mice. The biliary excretion
of ICG (0.4 µmol) was reduced by 90%, while the biliary excretion of
total GSH was decreased by 65% in Mdr2/
mice relative to wild-type mice. In contrast, the biliary excretion of
E217G (0.1 µmol) was increased by 30% in
Mdr2/ mice. These data indicate that the
absence of Mdr2 differentially influences the biliary excretion of
these organic anions and suggest that phospholipid vesicles and mixed
micelles in bile are essential for the biliary excretion of ICG.
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