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Biochem Biophys Res Commun. 2000 Oct 14;277(1):1-6.

Phenobarbital-elicited activation of nuclear receptor CAR in induction of cytochrome P450 genes.

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Pharmacogenetics Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709, USA.


Phenobarbital (PB) increases metabolic capability of hepatocytes by its ability to activate numerous genes encoding various xenochemical-metabolizing enzymes such as cytochrome P450s and specific transferases. More than 35 years since PB induction was first reported, the key nuclear receptor CAR that mediates the induction has now been identified, and the molecular/cellular mechanism involving multiple signal transduction pathways has begun to be unraveled. In response to PB exposure, CAR in the cytoplasm translocates into the nucleus, forms a heterodimer with the retinoid X receptor, and activates the PB response enhancer element leading to the concerted induction of numerous genes.

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