Induction of cytochrome P-450c and P-450d by metyrapone in the primary culture of rat hepatocytes |
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| Authors: | K Hirota T Kawanishi M Sunouchi Y Ohno A Takanaka Y Yamazoe R Kato Y Murakoshi |
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| Affiliation: | Department of Pharmacology, National Institute of Hygienic Sciences, Tokyo, Japan. |
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| Abstract: | The effects of metyrapone on qualitative changes in cytochrome P-450-dependent drug metabolizing activities in primary cultures of rat hepatocytes were investigated. Metyrapone apparently increased benzo(a)pyrene hydroxylation and maintained both ethoxycoumarin-O-deethylation and propoxycoumarin-O-depropylation, whereas it had little effect on methoxycoumarin-O-demethylation. Furthermore, P-450d (high spin type of P-448) as well as P-450c (low spin type of P-448) were induced by metyrapone, while P-450b and P-450e were not. In conclusion, metyrapone act as a 3-methylcholanthrene-like inducer in the primary cultures of rat hepatocytes. |
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