The nuclear pregnane X receptor regulates xenobiotic detoxification

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

The pregnane X receptor (PXR), which is a member of the nuclear receptor family of ligand-activated transcription factors, is an integral component of the body's defense mechanism against toxic xenobiotics. PXR is activated by a broad spectrum of lipophilic xenobiotics including prescription drugs, herbs, pesticides, endocrine disruptors and other environmental contaminants. The promiscuous ligand-binding properties of PXR are facilitated by the large volume and smooth shape of its ligand-binding pocket. PXR binds to DNA as a heterodimer with the 9-cis retinoic acid receptor (RXR) and regulates a large number of genes involved in the detoxification and excretion of toxic substances. Although PXR evolved to protect the body, its activation by various prescription drugs and herbs such as St. John's wort represents the molecular basis for an important class of drug-drug interactions. Assays that detect PXR activation can now be used to predict and prevent these drug-drug interactions.

Original languageEnglish (US)
JournalJournal of Nutrition
Volume133
Issue number7 SUPPL.
StatePublished - Jul 1 2003

Fingerprint

Xenobiotics
xenobiotics
receptors
Prescription Drugs
Poisons
Ligands
Drug Interactions
drug interactions
drugs
Retinoid X Receptors
Hypericum
Endocrine Disruptors
herbs
Defense Mechanisms
Cytoplasmic and Nuclear Receptors
Nuclear Family
Pesticides
Pharmaceutical Preparations
endocrine-disrupting chemicals
pregnane X receptor

Keywords

  • Cytochrome P450
  • Drug-drug interaction
  • Nuclear receptor
  • St. John's wort
  • Xenobiotic

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Food Science

Cite this

The nuclear pregnane X receptor regulates xenobiotic detoxification. / Kliewer, Steven A.

In: Journal of Nutrition, Vol. 133, No. 7 SUPPL., 01.07.2003.

Research output: Contribution to journalArticle

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