The Induction of CYP2B Proteins in Rodents by Phenobarbital-Like Inducers: What Has Been Discovered and What Remains to be Learned

Alan Anderson

Centre de recherche, L’Hôtel-Dieu de Québec, Québec G1R 2J6 Canada and Département de biologie, Université Laval, Québec G1K 7P4 Canada
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Cytochrome P450s (CYPs) are key enzymes of Phase I metabolism of xenobiotics and endobiotics in the liver, and many hepatic CYPs are inducible by xenobiotics. A striking example of inducible CYPs is furnished by the CYP2B proteins in rat and mouse liver, which are strongly induced by phenobarbital (PB). A 163-bp Sau3AI fragment in the CYP2B2 5’ flank confers PB inducibility on reporter genes in primary rat hepatocytes and has the properties of a transcriptional enhancer. This fragment is referred to as the PB response unit (PBRU). The purpose of this review is to summarize present understanding of the molecular mechanism whereby the PBRU confers PB responsiveness, and to examine what remains to be learned concerning the induction of CYP2B proteins (chiefly in rodents, but also in humans) by PB and PB-like inducers.

Keywords: Phenobarbital, induction, CYP2B, constitutive androstane receptor, rats, mice