Expression of aryl hydrocarbon receptor (AhR) and aryl hydrocarbon receptor nuclear translocator (Arnt) in adult rabbits known to be non-responsive to cytochrome P-450 1A1 (CYP1A1) inducers.
Induction of aryl hydrocarbon hydroxylase by aryl hydrocarbons occurs only in neonatal rabbits and not in adult rabbits [Kahl, G. F., Friederich, D. E., Bigelow, S. W., Okey, A. B. & Nebert, D. W. (1980) Dev. Pharmacol. Ther. 1,137-162]. In the present study, we isolated cDNA clones encoding aryl hydrocarbon receptor (AhR) and aryl hydrocarbon receptor nuclear translocator (Arnt) from adult rabbits. The deduced amino acid sequences of rabbit AhR and Arnt showed 80% and 94% identities with those of human AhR and Arnt, respectively. Rabbit AhR mRNA was predominantly expressed in the lung and liver. In contrast, rabbit Arnt mRNA was expressed at almost the same level in all tissues except for the heart, liver, and small intestine. Gel shift analysis showed that the AhR. Arnt complex could bind to the consensus xenobiotic-responsive element, which indicates that AhR expressed in adult rabbit liyers possessed binding activity to the consensus xenobiotic-responsive element in vitro, although aryl hydrocarbons did not induce the activity of AHH in adult rabbits. We propose that the incapability of adult rabbits to induce cytochrome P-450 1A1 (CYP1A1) is caused by factors other than AhR and Arnt.
Takahashi
Y
Y
Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Hokkaido University, Japan.
Nakayama
K
K
Shimojima
T
T
Itoh
S
S
Kamataki
T
T
D000367:Age Factors; D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D001483:Base Sequence; D003001:Cloning, Molecular; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D004790:Enzyme Induction; D015971:Gene Expression Regulation, Enzymologic; D008099:Liver / Q000378:metabolism; D046911:Macromolecular Substances; D008748:Methylcholanthrene / Q000737:chemistry; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D046911:Macromolecular Substances; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D014157:Transcription Factors; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D008748:Methylcholanthrene; D019363:Cytochrome P-450 CYP1A1