Cell Biology and Toxicology

, Volume 18, Issue 4, pp 221–233

The drug efflux pump MRP2: Regulation of expression in physiopathological situations and by endogenous and exogenous compounds

  • L. Payen
  • L. Sparfel
  • A. Courtois
  • L. Vernhet
  • A. Guillouzo
  • O. Fardel
Article

DOI: 10.1023/A:1016020626941

Cite this article as:
Payen, L., Sparfel, L., Courtois, A. et al. Cell Biol Toxicol (2002) 18: 221. doi:10.1023/A:1016020626941

Abstract

The multidrug resistance-associated protein 2 (MRP2) is an ATP-binding cassette transporter involved in biliary, renal, and intestinal secretion of numerous organic anions, including endogenous compounds such as bilirubin and exogenous compounds such as drugs and toxic chemicals. Its expression can be modulated in various physiopathological situations, notably being markedly decreased during liver cholestasis and upregulated in some cancerous tissues. In addition, MRP2 levels are altered in hepatocytes in response to hormones such as glucocorticoids and to structurally unrelated drugs such as rifampicin, phenobarbital, ritonavir, and cisplatin. The chemical carcinogen 2-acetylaminofluorene and chemopreventive agents such as oltipraz and sulforaphane also markedly increased MRP2 expression in liver parenchymal cells. Interestingly, most of the chemical inducers of MRP2 act on drug-metabolizing enzymes, indicating a coordinated regulation of these detoxifying proteins; cellular mechanisms involved are, at least partly, common and may be related to nuclear hormone receptors such as the pregnane X receptor. Owing to the major role played by MRP2 in elimination of drugs and endogenous compounds, modulation of its expression may lead to adverse effects or to changes in drug pharmacokinetics.

hepatocytes hormone multidrug resistance-associated protein 2 pregnane X receptor xenobiotic 

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • L. Payen
    • 1
  • L. Sparfel
    • 1
  • A. Courtois
    • 1
  • L. Vernhet
    • 1
  • A. Guillouzo
    • 1
  • O. Fardel
    • 1
  1. 1.Faculté de PharmacieINSERM U456RennesFrance