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Vol. 302, Issue 2, 407-415, August 2002
Graduate Center for Toxicology, University of Kentucky, Lexington,
Kentucky
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.
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