LIVER MICROSOMAL CYTOCHROME P-450-DEPENDENT O-DEALKYLATION REACTION IN VARIOUS ANIMALS
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概要
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Liver microsomal O-dealkylation activity was determined using O-methyl, O-ethyl and O-propyl derivatives of p-nitrophenol, 7-hydroxycoumarin (umbelliferon) and 7-hydroxyphenoxazone (resorufin) as substrates. Microsomal O-dealkylation activities of p-nitrophenol and 7-hydroxycoumarin O-alkyl derivatives were of similar levels, but the activities of 7-hydroxyphenoxazone O-alkyl derivatives were very low compared with those of other substrates. Pretreatment of rats with β-naphthoflavone resulted in the preferential increase of O-deethylation and O-depropylation activities regardless of the ring structure of the substrates, and the ratio of O-deethylation and O-depropylation activities to that of O-demethylation increased markedly. On the other hand, the O-dealkylase activity of all substrates increased generally upon pretreatment of the rats with phenobarbital, but the ratio of O-deethylase or O-depropylase activity to that of O-demethylase in the pretreated rats was not very different from that of the untreated animals. Hexobarbital inhibited competitively the O-dealkylation activity in control and phenobarbital-pretreated rat microsomes. On the other hand, the O-dealkylase activity in microsomes obtained from β-naphthoflavone-pretreated rats was inhibited remarkably by α-naphthoflavone, but not in microsomes prepared from untreated and phenobarbital-pretreated rats. Based on these results, this report discusses the relationship between the alteration of O-dealkylation activity and the composition change of cytochrome P-450 in microsomal membrane. Species differences in the substrate specificity of the O-dealkylation reaction and in the responsiveness of the animals to typical inducers were also observed using liver microsomes obtained from several animals under various conditions.
- 社団法人 日本薬理学会の論文
著者
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Matsubara Takashi
Shionogi Research Laboratories Shionogi & Co. Ltd.
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OTSUBO Shigemi
Shionogi Research Laboratories, Shionogi & Co., Ltd.
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YOSHIHARA Emiko
Shionogi Research Laboratories, Shionogi & Co., Ltd.
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Matsubara Takashi
Shionogi Research Laboratories
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Yoshihara Emiko
Shionogi Research Laboratories
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YOSHIHARA Emiko
Shionogi Research Laboratories, Shionogi & Co. Ltd.
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