Induction of drug metabolism by nuclear receptor CAR: molecular mechanisms and implications for drug research.
Recent findings indicate that induction of drug metabolism is regulated by activation of specific members of the nuclear receptor gene family. This minireview deals with the mechanisms by which phenobarbital and phenobarbital-type chemicals induce cytochrome P450 and other genes, and summarises the knowledge on the role of the constitutively active receptor CAR in the induction process. The potential implications of CAR-mediated induction for drug research and possible uses of CAR are also discussed.
Masahiko
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Pharmacogenetics Section, Laboratory of Reproductive and Developmental Toxicology, NIEHS, National Institutes of Health, Research Triangle Park, NC 27709, USA.
Honkakoski
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P
D000818:Animals; D000927:Anticonvulsants / Q000378:metabolism* / Q000494:pharmacology; D001189:Aryl Hydrocarbon Hydroxylases; D001702:Biopharmaceutics; D002626:Chemistry, Pharmaceutical; D000090702:Constitutive Androstane Receptor; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D010089:Oxidoreductases, N-Demethylating / Q000187:drug effects / Q000378:metabolism; D010634:Phenobarbital / Q000378:metabolism* / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000378:metabolism*; D020218:Response Elements / Q000502:physiology*; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors
D000927:Anticonvulsants; D000090702:Constitutive Androstane Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators; D014157:Transcription Factors; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D010634:Phenobarbital