Differences in Cytochrome P450 and Nuclear Receptor mRNA Levels in Liver and Small Intestines between SD and DA Rats

This study aimed to clarify the differences in mRNA levels of cytochrome P450 (CYP) isoforms and nuclear receptors between Dark Agouti (DA) and Sprague-Dawley (SD) rats which are animal models for poor metabolizers and extensive metabolizers for CYP2D6, respectively. Using liver and small intestine...

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Bibliographic Details
Published in:DRUG METABOLISM AND PHARMACOKINETICS 2008-01, Vol.23 (3), p.196-206
Main Authors: Kawase, Atsushi, Fujii, Akiyuki, Negoro, Makiko, Akai, Ryosuke, Ishikubo, Miki, Komura, Hiroshi, Iwaki, Masahiro
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Chromatography, High Pressure Liquid
Cytochrome P-450 Enzyme System - genetics
cytochrome P450
DA rat
Female
Intestine, Small - enzymology
Intestine, Small - metabolism
Liver - enzymology
Liver - metabolism
Male
Microsomes - enzymology
Microsomes - metabolism
Molecular Sequence Data
nuclear receptor
Organ Specificity
Protein Isoforms
Rats
Rats, Inbred Strains
Rats, Sprague-Dawley
Receptors, Cytoplasmic and Nuclear - genetics
RNA, Messenger - genetics
SD rat
Species Specificity
strain difference
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Summary:This study aimed to clarify the differences in mRNA levels of cytochrome P450 (CYP) isoforms and nuclear receptors between Dark Agouti (DA) and Sprague-Dawley (SD) rats which are animal models for poor metabolizers and extensive metabolizers for CYP2D6, respectively. Using liver and small intestine tissues of both rat strains, we investigated the mRNA levels of CYP1A, 2A, 2B, 2C, 2D, 2E, and 3A subfamilies and nuclear receptors which regulate the transcription of CYP isoforms. In the liver, male DA rats showed a low CYP2D2 mRNA level but high mRNA levels of CYP3A1, 3A2, and 1A1 compared to SD rats. No significant difference was noted in other CYP isoforms. The mRNA levels of CAR were higher in DA rats than those in SD rats. In small intestine, the mRNA levels of CYP isoforms and nuclear receptors exhibited no significant strain differences. In addition, the activity of CYP3A in small intestinal microsome did not differ between SD and DA rats. Female DA rats exhibited higher mRNA levels of CYP3A1, 3A2, and 2B1 in the liver than female SD rats. In conclusion, the mRNA levels of CYP3A1 and 3A2 isoforms and CAR in the liver but not in the small intestines were different between DA and SD rats in both sexes.
ISSN:1347-4367
1880-0920
DOI:10.2133/dmpk.23.196