Induction of cytochrome P-450c and P-450d by metyrapone in the primary culture of rat hepatocytes.
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.
Hirota
K
K
Department of Pharmacology, National Institute of Hygienic Sciences, Tokyo, Japan.
Kawanishi
T
T
Sunouchi
M
M
Ohno
Y
Y
Takanaka
A
A
Yamazoe
Y
Y
Kato
R
R
Murakoshi
Y
Y
D000818:Animals; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008797:Metyrapone / Q000494:pharmacology*; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010634:Phenobarbital; D008797:Metyrapone