文章基本信息

标题：Characterization of Microsomal Alcohol Oxygenase Catalyzing the Oxidation of 7-Hydroxy-Δ8-tetrahydrocannabinol to 7-Oxo-Δ8-tetrahydrocannabinol in Rat Liver
本地全文：下载
作者：Tamihide MATSUNAGA ; Kinya SHIBAYAMA ; Shinsuke HIGUCHI 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2000
卷号：23
期号：1
页码：43-46
DOI：10.1248/bpb.23.43
出版社：The Pharmaceutical Society of Japan
摘要：The formation of 7-oxo-Δ⁸-tetrahydrocannabinol (7-oxo-Δ⁸-THC) from 7β-hydroxy-Δ⁸-THC was found in hepatic microsomes of rats. The activity was stereoselective and about 3-fold higher than that from 7α-hydroxy-Δ⁸-THC. The oxidative activity of 7α- and 7β-hydroxy-Δ⁸-THC to 7-oxo-Δ⁸-THC was significantly higher in male than in female, and significantly enhanced by both dexamethasone and phenobarbital, and then inhibited up to about 20% of the control value by antibody against P450GPF-B, presumably a member of the 3A subfamily, a major enzyme responsible for the formation of 7-oxo-Δ⁸-THC in guinea pigs. This antibody also inhibited the formation of 7α- and 7β-hydroxy-Δ⁸-THC, and 7-oxo-Δ⁸-THC from Δ⁸-THC by hepatic microsomes of rats. These results indicate that there is a sex-related difference in the oxidatio of 7-hydroxy-Δ⁸-THC to 7-oxo-Δ⁸-THC and the reaction is mainly catalyzed by P450 enzyme(s) beloging to the 3A subfamily as major enzyme(s) of microsomal alcohol oxygenase in rats.
关键词：7-hydroxy-Δ8-tetrahydrocannabinol;microsomal alcohol oxygenase;CYP3A;7-oxo-Δ8-tetrahydrocannabinol;cytochrome P450;sex-related difference