Single nucleotide polymorphisms in multidrug resistance associated protein 2 (MRP2/ABCC2): its impact on drug disposition

Adv Drug Deliv Rev. 2002 Nov 18;54(10):1311-31. doi: 10.1016/s0169-409x(02)00075-3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bile / metabolism
  • Biological Transport / genetics
  • Drug Resistance, Multiple / genetics
  • Humans
  • Liver / metabolism
  • Membrane Transport Proteins*
  • Multidrug Resistance-Associated Proteins / biosynthesis
  • Multidrug Resistance-Associated Proteins / genetics*
  • Pharmaceutical Preparations
  • Polymorphism, Single Nucleotide*
  • Rats
  • Substrate Specificity
  • Tissue Distribution

Substances

  • Membrane Transport Proteins
  • Multidrug Resistance-Associated Proteins
  • Pharmaceutical Preparations
  • multidrug resistance-associated protein 2