Regulation of hepatic transporters by xenobiotic receptors

Curr Drug Metab. 2005 Aug;6(4):309-28. doi: 10.2174/1389200054633826.


Chemicals that increase expression of phase-I and -II biotransformation enzymes in liver, as well as enhance hepatic uptake and biliary excretion are often referred to as microsomal enzyme inducers (MEIs). Early studies suggested that drug metabolism might be coordinately regulated along with drug efflux from hepatocytes as a means for the liver to rid itself of foreign chemicals. Since then, the identification and characterization of nuclear receptors (NRs) has aided in understanding of how various MEIs enhance xeniobiotic uptake, biotransformation, and excretion. In addition, the NRs by which several classes of MEIs induce phase-I and -II drug metabolizing enzymes have been elucidated (i.e. AHR, CAR, PXR, PPARalpha, Nrf2). Several transporter families which mediate uptake of chemicals into liver and excretion of chemicals from liver into blood and/or bile have been cloned and identified. In general, the organic anion transporting polypeptide family (Oatps) along with Organic cation transporter 1 (Oct1) and Organic anion transporter 2 mediate uptake of a large number of xenobiotics from blood into liver. Conversely, Multidrug resistance proteins (Mdrs), Multidrug resistance-associated proteins (Mrps), and Breast cancer resistance protein (Bcrp) mediate efflux of xenobiotics from liver into bile or blood. Recent studies have demonstrated that MEIs increase expression of various Oatps, Mrps, and Mdrs in liver, and some occur via activation of nuclear receptors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / metabolism*
  • Enzyme Induction / drug effects
  • Genes, MDR / physiology
  • Humans
  • Liver / metabolism*
  • Mice
  • Microsomes, Liver / metabolism
  • Pharmaceutical Preparations / metabolism
  • Rats
  • Receptors, Drug / physiology*
  • Transcription Factors / metabolism
  • Xenobiotics / metabolism*
  • Xenobiotics / pharmacokinetics


  • Carrier Proteins
  • Pharmaceutical Preparations
  • Receptors, Drug
  • Transcription Factors
  • Xenobiotics