Secretion of Organic Anions by Hepatocytes: Involvement of Homologues of the Multidrug Resistance Protein

ABSTRACT

The canalicular multispecific organic onion transporter (cMOAT) is one of at least four ATP-dependent transport systems identified so far in the canalicular membrane domain. Using mutant rat strains that lack organic anion secretion, the substrate specificity of cMOAT has been characterized. cMOAT appears to be responsible for the elimination of amphipathic anionic conjugates formed by phase II conjugation. Very recently it has been shown that the hepatocyte-specific homologue (MRP2) of the multidrug resistance protein (MRP1) functions as cMOAT in the canalicular membrane, whereas MRP I is present on the lateral membrane only at very low levels in quiescent cells. The defective excretion of organic anions in TR^- rat livers is caused by the total absence of mrp2 due to a deletion of one nucleotide in the mrp2 gene. In conclusion, the liver-specific mrp2/MRP2, a new member of the ATP-binding cassette superfamily, appears to function as cMOAT in the hepatobiliary secretion of organic anions.

KEY WORDS

ATP-dependent transport - mutant rats - regulation - ABC-superfamily - glutathione