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Drug Metab Pharmacokinet ; 23(3): 196-206, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18574324

RESUMO

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.


Assuntos
Sistema Enzimático do Citocromo P-450/genética , Intestino Delgado , Fígado , RNA Mensageiro/genética , Receptores Citoplasmáticos e Nucleares/genética , Animais , Sequência de Bases , Cromatografia Líquida de Alta Pressão , Feminino , Intestino Delgado/enzimologia , Intestino Delgado/metabolismo , Fígado/enzimologia , Fígado/metabolismo , Masculino , Microssomos/enzimologia , Microssomos/metabolismo , Dados de Sequência Molecular , Especificidade de Órgãos , Isoformas de Proteínas , Ratos , Ratos Endogâmicos , Ratos Sprague-Dawley , Especificidade da Espécie
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