Phenobarbital-elicited activation of nuclear receptor CAR in induction of cytochrome P450 genes.
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.
Zelko
I
I
Pharmacogenetics Section, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709, USA.
Negishi
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M
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D001483:Base Sequence; D000090702:Constitutive Androstane Receptor; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D004790:Enzyme Induction / Q000187:drug effects*; D006801:Humans; D008969:Molecular Sequence Data; D010634:Phenobarbital / Q000494:pharmacology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D020218:Response Elements / Q000235:genetics; D013256:Steroids / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism*
D000090702:Constitutive Androstane Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D013256:Steroids; D014157:Transcription Factors; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital