Regulation of expression of the multidrug resistance-associated protein 2 (MRP2) and its role in drug disposition.
The multidrug resistance protein 2 (MRP2; ABCC2) is an ATP-binding cassette transporter accepting a diverse range of substrates, including glutathione, glucuronide, and sulfate conjugates of many endo- and xenobiotics. MRP2 generally performs excretory or protective roles, and it is expressed on the apical domain of hepatocytes, enterocytes of the proximal small intestine, and proximal renal tubular cells, as well as in the brain and the placenta. MRP2 is regulated at several levels, including membrane retrieval and reinsertion, translation, and transcription. In addition to transport of conjugates, MRP2 transports cancer chemotherapeutics, uricosurics, antibiotics, leukotrienes, glutathione, toxins, and heavy metals. Several mutagenesis studies have described critical residues for substrate binding and various naturally occurring mutations that eliminate MRP2 expression or function. MRP2 is important clinically as it modulates the pharmacokinetics of many drugs, and its expression and activity are also altered by certain drugs and disease states.
Graduate Center for Toxicology, University of Kentucky, Room 306, Health Science Building, Lexington, KY 40536-0305, USA.
Phillip M
PM
Gerk
Mary
M
Vore
D000595:Amino Acid Sequence; D000818:Animals; D018432:Drug Resistance, Multiple / Q000235:genetics*; D005091:Exons; D005786:Gene Expression Regulation; D006801:Humans; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000737:chemistry / Q000235:genetics*; D010641:Phenotype; D010802:Phylogeny; D011401:Promoter Regions, Genetic
D026901:Membrane Transport Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C000715087:ABCC2 protein, human; C421109:multidrug resistance-associated protein 1