EFFECT OF TYPE I COMPOUNDS ON <I>P</I>-HYDROXYLATION OF ANILINE IN VITRO
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概要
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During the past fifteen years, it has become evident that a variety of lipid soluble drugs such as aniline, aminopyrine and hexobarbital are oxidized by NADPH-dependent enzymes in hepatic microsomes (1-4). Cytochrome(s) P-450 plays a critical role as the terminal oxidase in the metabolism of drugs, steroids and heme (5-7). It is generally accepted that the hepatic drug-metabolizing enzyme system has few specificities for substrates but recent studies have suggested the existence of more than two microsomal enzymes which metabolize the drugs (8, 9).<BR> On the other hand, the addition of various substrates of microsomal mixed-function oxidase system to aerobic liver microsomes causes two types of spectral change. One class of spectral change (termed type I) is characterized by the appearance of a trough at 420 mμ and an absorption peak at 385 mμ. Aminopyrine, hexobarbital, chlorpromazine, SKF 525-A and DDT cause type I spectral change. Another class of spectral change (termed type II) is characterized by the appearance of a trough at 392 mμ and an absorption peak at 430 mμ. Aniline, nicotinamide, pyridine and <I>p</I>-aminophenol cause type II spectral change (10).<BR> Drug interaction with endoplasmic reticulum occurs not only to constitute enzymesubstrate complex but also to modify the physical properties, amounts, composition and turnover of constitutive membrane components (11). At present aniline is thought to bind to the CO-binding site of cytochrome P-450, whereas aminopyrine or hexobarbital is thought to bind to the lipids of the endoplasmic reticulum or hydrophobic region cytochrome P-450 (12).<BR> The present paper concerns the effects of type I binders such as aminopyrine, hexobarbital and chlorpromazine on <I>p</I>-hydroxylation of aniline in vitro.
- 公益社団法人 日本薬理学会の論文
著者
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Kinoshita Go
Department Of Applied Analysis And Complex Dynamical Systems Graduate School Of Informatics Kyoto Un
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SHIOHARA Eiko
Department of Pharmacology, Faculty of Medicine, Shinshu University
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NAKANISHI Suehiro
Department of Pharmacology, Faculty of Medicine, Shinshu University
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Tsukada Miyoko
Department Of Pharmacology Shinshu University School Of Medicine
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