title: The tangle of nuclear receptors that controls xenobiotic metabolism and transport: crosstalk and consequences.
abstract: The expression of many genes involved in xenobiotic/drug metabolism and transport is regulated by at least three nuclear receptors or xenosensors: aryl hydrocarbon receptor (AhR), constitutive androstane receptor (CAR), and pregnane X receptor (PXR). These receptors establish crosstalk with other nuclear receptors or transcription factors controlling signaling pathways that regulate the homeostasis of bile acids, lipids, glucose, inflammation, vitamins, hormones, and others. These crosstalks are expected to modify profoundly our vision of xenobiotic/drug disposition and toxicity. They provide molecular mechanisms to explain how physiopathological stimuli affect xenobiotic/drug disposition, and how xenobiotics/drugs may affect physiological functions and generate toxic responses. In addition, the possibility that xenosensors may control other signaling pathways opens the way to new pharmacological opportunities.
authors.affiliation: INSERM U632, Univ Montpellier 1, Montpellier, France. pascussi@montp.inserm.fr
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Pascussi
authors.forename: Sabine
authors.initials: S
authors.lastname: Gerbal-Chaloin
authors.forename: Cédric
authors.initials: C
authors.lastname: Duret
authors.forename: Martine
authors.initials: M
authors.lastname: Daujat-Chavanieu
authors.forename: Marie-José
authors.initials: MJ
authors.lastname: Vilarem
authors.forename: Patrick
authors.initials: P
authors.lastname: Maurel
mesh_terms: D001692:Biological Transport / Q000502:physiology; D005786:Gene Expression Regulation; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism; D015262:Xenobiotics / Q000009:adverse effects / Q000493:pharmacokinetics*
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D015262:Xenobiotics