Single nucleotide polymorphisms in multidrug resistance associated protein 2 (MRP2/ABCC2): its impact on drug disposition.
Multidrug resistance associated protein 2 (MRP2/ABCC2), expressed on the bile canalicular membrane, plays an important role in the biliary excretion of various kinds of substrates. In addition, MRP2 is also expressed on the apical membrane of epithelial cells such as enterocytes. It is possible that the inter-individual difference in the function of MRP2 affects the drug disposition. In the present article, we will summarize the physiological and pharmacological role of MRP2, particularly focusing on the factors affecting its transport function such as single nucleotide polymorphisms and/or the induction/down regulation of this transporter. Mutations found in patients suffering from the Dubin-Johnson syndrome, along with the amino acid residues which are involved in supporting the transport activity of MRP2, are also summarized.
Suzuki
Hiroshi
H
School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. hsuzuki@mol.f.u-tokyo.ac.jp
Sugiyama
Yuichi
Y
D000818:Animals; D001646:Bile / Q000378:metabolism; D001692:Biological Transport / Q000235:genetics; D018432:Drug Resistance, Multiple / Q000235:genetics; D006801:Humans; D008099:Liver / Q000378:metabolism; D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000096:biosynthesis / Q000235:genetics*; D004364:Pharmaceutical Preparations; D020641:Polymorphism, Single Nucleotide; D051381:Rats; D013379:Substrate Specificity; D014018:Tissue Distribution
D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D004364:Pharmaceutical Preparations; C000715087:ABCC2 protein, human