Phenobarbital induces cytochrome P4501A2 hnRNA, mRNA and protein in the liver of C57BL/6J wild type and aryl hydrocarbon receptor knock-out mice.
The aryl hydrocarbon receptor mediates the transcriptional response to a variety of hydrocarbons of members of the aryl hydrocarbon gene battery. Phenobarbital does not bind the aryl hydrocarbon receptor with high affinity but induces, in liver cells, expression of cytochrome P4501A. Using both wild type and aryl hydrocarbon receptor knock out C57BL/6J mice, we demonstrate that phenobarbital induced hnRNA, mRNA and protein for the cytochrome P-4501A2 gene in the presence or absence of the aryl hydrocarbon receptor. Using the DNA binding site for the aryl hydrocarbon receptor as a probe, gel retardation analyses showed that phenobarbital treatment induced protein binding, regardless of the presence of the aryl hydrocarbon receptor.
Corcos
L
L
INSERM U456, Faculté de Pharmacie, Rennes, France. laurent.corcos@univ-rennes1.fr
Marc
N
N
Wein
S
S
Fautrel
A
A
Guillouzo
A
A
Pineau
T
T
D000818:Animals; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics* / Q000378:metabolism; D018757:GABA Modulators / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology*; D012332:RNA, Heterogeneous Nuclear; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*
D018757:GABA Modulators; D009687:Nuclear Proteins; D012332:RNA, Heterogeneous Nuclear; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D019388:Cytochrome P-450 CYP1A2; D010634:Phenobarbital