The tangle of nuclear receptors that controls xenobiotic metabolism and transport: crosstalk and consequences.
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.
Pascussi
Jean-Marc
JM
INSERM U632, Univ Montpellier 1, Montpellier, France. pascussi@montp.inserm.fr
Gerbal-Chaloin
Sabine
S
Duret
Cédric
C
Daujat-Chavanieu
Martine
M
Vilarem
Marie-José
MJ
Maurel
Patrick
P
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*
D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D015262:Xenobiotics