Regulation of drug-metabolizing enzymes by xenobiotic receptors: PXR and CAR

Adv Drug Deliv Rev. 2010 Oct 30;62(13):1238-49. doi: 10.1016/j.addr.2010.08.006. Epub 2010 Aug 17.


Drug-metabolizing enzymes (DMEs) and transporters play pivotal roles in the disposition and detoxification of numerous foreign and endogenous chemicals. To accommodate chemical challenges, the expression of many DMEs and transporters is up-regulated by a group of ligand-activated transcription factors namely nuclear receptors (NRs). The importance of NRs in xenobiotic metabolism and clearance is best exemplified by the most promiscuous xenobiotic receptors: pregnane X receptor (PXR, NR1I2) and constitutive androstane/activated receptor (CAR, NR1I3). Together, these two receptors govern the inductive expression of a largely overlapping array of target genes encoding phase I and II DMEs, and drug transporters. Moreover, PXR and CAR also represent two distinctive mechanisms of NR activation, whereby CAR demonstrates both constitutive and ligand-independent activation. In this review, recent advances in our understanding of PXR and CAR as xenosensors are discussed with emphasis placed on the differences rather than similarities of these two xenobiotic receptors in ligand recognition and target gene regulation.

Publication types

  • Review

MeSH terms

  • Animals
  • Biological Transport
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Constitutive Androstane Receptor
  • Gene Expression Regulation
  • Humans
  • Inactivation, Metabolic* / genetics
  • Ligands
  • Pregnane X Receptor
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism*
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Receptors, Steroid / genetics
  • Receptors, Steroid / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Xenobiotics / metabolism*


  • Carrier Proteins
  • Constitutive Androstane Receptor
  • Ligands
  • NR1I2 protein, human
  • NR1I3 protein, human
  • Pregnane X Receptor
  • Receptors, Aryl Hydrocarbon
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Steroid
  • Transcription Factors
  • Xenobiotics