The tangle of nuclear receptors that controls xenobiotic metabolism and transport: crosstalk and consequences

Annu Rev Pharmacol Toxicol. 2008;48:1-32. doi: 10.1146/annurev.pharmtox.47.120505.105349.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biological Transport / physiology
  • Gene Expression Regulation*
  • Homeostasis / physiology
  • Humans
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Signal Transduction / physiology
  • Transcription Factors / metabolism
  • Xenobiotics / adverse effects
  • Xenobiotics / pharmacokinetics*

Substances

  • Receptors, Cytoplasmic and Nuclear
  • Transcription Factors
  • Xenobiotics