Regulation of xenobiotic and bile acid metabolism by the nuclear pregnane X receptor

Steven A. Kliewer, Timothy M. Willson

Research output: Contribution to journalArticle

165 Citations (Scopus)

Abstract

The nuclear pregnane X receptor (PXR; NR1I2) is an integral component of the body's defense mechanism against chemical insult (chemoprotection). PXR is activated by a diverse array of lipophilic chemicals, including xenobiotics and endogenous substances, and regulates the expression of cytochromes P450, conjugating enzymes, and transporters involved in the metabolism and elimination of these potentially harmful chemicals from the body. Among the chemicals that bind and activate PXR is the toxic bile acid lithocholic acid; activation of PXR, in turn, protects against the severe liver damage caused by this bile acid.?? Thus, PXR serves as a physiological sensor of lithocholic acid and perhaps other bile acids and coordinately regulates genes involved in their detoxification. Interestingly, both the antibiotic rifampicin and the herbal antidepressant St. John's wort activate PXR and have anticholestatic properties, which suggests that more potent, selective PXR agonists may be useful in the treatment of biliary cholestasis or other diseases characterized by the accumulation of bile acids or other toxins in the liver.

Original languageEnglish (US)
Pages (from-to)359-364
Number of pages6
JournalJournal of Lipid Research
Volume43
Issue number3
StatePublished - 2002

Fingerprint

Xenobiotics
Bile Acids and Salts
Metabolism
Lithocholic Acid
Liver
Cytochrome P-450 Enzyme System
Hypericum
Detoxification
Poisons
Cholestasis
Rifampin
Antidepressive Agents
Genes
Chemical activation
Anti-Bacterial Agents
pregnane X receptor
Sensors

Keywords

  • Cholestasis
  • Cytochrome P450
  • Drug-drug interaction
  • Farnesoid X receptor
  • Lithocholic acid
  • Nuclear receptor

ASJC Scopus subject areas

  • Endocrinology

Cite this

Regulation of xenobiotic and bile acid metabolism by the nuclear pregnane X receptor. / Kliewer, Steven A.; Willson, Timothy M.

In: Journal of Lipid Research, Vol. 43, No. 3, 2002, p. 359-364.

Research output: Contribution to journalArticle

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