title: Nuclear receptors PXR and CAR: implications for drug metabolism regulation, pharmacogenomics and beyond.
abstract: BACKGROUND
  'Orphan' nuclear receptors belong to the nuclear receptor (NR) superfamily of transcriptional factors. Binding of ligands to these receptors results in the recruitment of the co-activators, thereby regulating the expression of cognate target genes.
  
  
  METHODS
  This review discusses the transcriptional regulation of P450 genes by two major xenobiotic nuclear receptors, pregnane X receptor (PXR) and constitutive androstane receptor (CAR). Additional PXR and CAR target genes include those encoded for UDP-glucuronosyltransferases, glutathione S-transferases, sulfotransferases and drug transporters. The authors discuss the involvement of PXR and CAR in endobiotic metabolism. They also review the polymorphisms of PXR and CAR.
  
  
  CONCLUSIONS
  PXR and CAR are both xenobiotic and endobiotic receptors. A remarkably diverse set of chemicals can activate PXR and CAR. There is significant cross-talk among xenobiotic receptors. Future studies are needed to focus on the polymorphisms of the nuclear receptors and the complex regulatory networks among nuclear receptors. Considerations should be given while designing PXR- or CAR-targeting pharmaceutics to avoid adverse drug effects. In the meantime, due to the diverse functions of PXR and CAR, agonists or antagonists for these receptors may have therapeutic potentials in managing certain diseases and enhancing therapeutic indexes.
authors: Zhejiang University, College of Pharmaceutical Sciences, Department of Pharmaceutical Analysis and Drug Metabolism, Hangzhou 310058, China.
authors: Xiaojuan
authors: X
authors: Chai
authors: Su
authors: S
authors: Zeng
authors: Wen
authors: W
authors: Xie
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D001692:Biological Transport; D000090702:Constitutive Androstane Receptor; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008658:Inactivation, Metabolic; D050356:Lipid Metabolism / Q000187:drug effects; D010597:Pharmacogenetics; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism*; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015262:Xenobiotics / Q000378:metabolism
chemical_list: D001647:Bile Acids and Salts; D000090702:Constitutive Androstane Receptor; D000077297:Pregnane X Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D014157:Transcription Factors; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase; D015238:Sulfotransferases; D005947:Glucose