Effect of phenobarbital on hepatic CYP1A1 and CYP1A2 in the Ahr-null mouse.
Studies have suggested that phenobarbital (PB) induces members of the CYP1A subfamily by both transcriptional and post-transcriptional mechanisms. Using the Ahr -/- mice, we examined the induction of CYP1A1 and CYP1A2 by PB. CYP1A2 mRNA and protein were induced by PB in the null mice, suggesting that CYP1A2 is regulated by PB by a mechanism independent of the aryl hydrocarbon receptor (AHR). In contrast, the regulation of CYP1A1 is highly dependent on the AHR.
Zaher
H
H
Laboratory of Metabolism, National Cancer Institute, Bethesda, MD 20892, USA.
Yang
T J
TJ
Gelboin
H V
HV
Fernandez-Salguero
P
P
Gonzalez
F J
FJ
D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis*; D004790:Enzyme Induction; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D010634:Phenobarbital / Q000494:pharmacology*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D018336:Receptors, Aryl Hydrocarbon / Q000172:deficiency / Q000502:physiology*; D014158:Transcription, Genetic
D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D010634:Phenobarbital