PXR and CAR: Nuclear Receptors which Play a Pivotal Role in Drug Disposition and Chemical Toxicity
- 1 January 2006
- journal article
- research article
- Published by Taylor & Francis in Drug Metabolism Reviews
- Vol. 38 (3) , 515-597
- https://doi.org/10.1080/03602530600786232
Abstract
Xenobiotic metabolism and detoxification is regulated by receptors (e.g., PXR, CAR) whose characterization has contributed significantly to our understanding of drug responses in humans. Technologies facilitating the screening of compounds for receptor interactions provide valuable tools applicable in drug development. Most use in vitro systems or mice humanized for receptors in vivo. In vitro assays are limited by the reporter systems and cell lines chosen and are uninformative about effects in vivo. Humanized mouse models provide novel, exciting ways of understanding the functions of these genes. This article evaluates these technologies and current knowledge on PXR/CAR-mediated regulation of gene expression.Keywords
This publication has 209 references indexed in Scilit:
- Pregnane X receptor-agonists down-regulate hepatic ATP-binding cassette transporter A1 and scavenger receptor class B type IBiochemical and Biophysical Research Communications, 2005
- Impaired nuclear translocation of CAR in hepatic preneoplastic lesions: Association with an attenuated CYP2B induction by phenobarbitalFEBS Letters, 2005
- Steroid and xenobiotic receptor (SXR), cytochrome P450 3A4 and multidrug resistance gene 1 in human adult and fetal tissuesMolecular and Cellular Endocrinology, 2005
- Molecular dynamics simulations of the human CAR ligand-binding domain: deciphering the molecular basis for constitutive activityJournal of Molecular Modeling, 2004
- PXR and the regulation of apoA1 and HDL-cholesterol in rodentsPharmacological Research, 2004
- Nuclear Receptors Constitutive Androstane Receptor and Pregnane X Receptor Activate a Drug-responsive Enhancer of the Murine 5-Aminolevulinic Acid Synthase GeneJournal of Biological Chemistry, 2003
- Role of the Hepatocyte Nuclear Factor 4α in Control of the Pregnane X Receptor During Fetal Liver DevelopmentHepatology, 2003
- Benzoate X Receptors α and β Are Pharmacologically Distinct and Do Not Function as Xenobiotic ReceptorsPublished by Elsevier ,2002
- St John's Wort increases expression of P‐glycoprotein: Implications for drug interactionsBritish Journal of Clinical Pharmacology, 2002
- Interleukin-6 Negatively Regulates the Expression of Pregnane X Receptor and Constitutively Activated Receptor in Primary Human HepatocytesBiochemical and Biophysical Research Communications, 2000