Matsunaga T, Shibayama K, Higuchi S, Tanaka H, Watanabe K, Yamamoto I
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
Biol Pharm Bull. 2000 Jan;23(1):43-6. doi: 10.1248/bpb.23.43.
The formation of 7-oxo-delta8-tetrahydrocannabinol (7-oxo-delta8-THC) from 7beta-hydroxy-delta8-THC was found in hepatic microsomes of rats. The activity was stereoselective and about 3-fold higher than that from 7alpha-hydroxy-delta8-THC. The oxidative activity of 7alpha- and 7beta-hydroxy-delta8-THC to 7-oxo-delta8-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-delta8-THC in guinea pigs. This antibody also inhibited the formation of 7alpha- and 7beta-hydroxy-delta8-THC, and 7-oxo-delta8-THC from delta8-THC by hepatic microsomes of rats. These results indicate that there is a sex-related difference in the oxidation of 7-hydroxy-delta8-THC to 7-oxo-delta8-THC and the reaction is mainly catalyzed by P450 enzyme(s) belonging to the 3A subfamily as major enzyme(s) of microsomal alcohol oxygenase in rats.
在大鼠肝微粒体中发现了由7β-羟基-δ8-四氢大麻酚（7β-hydroxy-delta8-THC）形成7-氧代-δ8-四氢大麻酚（7-oxo-delta8-THC）的过程。该活性具有立体选择性，且比由7α-羟基-δ8-四氢大麻酚形成7-氧代-δ8-四氢大麻酚的活性高约3倍。7α-和7β-羟基-δ8-四氢大麻酚氧化生成7-氧代-δ8-四氢大麻酚的活性在雄性大鼠中显著高于雌性大鼠，地塞米松和苯巴比妥均可显著增强该活性，然后用抗P450GPF-B抗体将其抑制至对照值的约20%，P450GPF-B可能是3A亚家族的成员，是豚鼠中负责形成7-氧代-δ8-四氢大麻酚的主要酶。该抗体还抑制了大鼠肝微粒体由δ8-四氢大麻酚形成7α-和7β-羟基-δ8-四氢大麻酚以及7-氧代-δ8-四氢大麻酚的过程。这些结果表明，7-羟基-δ8-四氢大麻酚氧化生成7-氧代-δ8-四氢大麻酚的过程存在性别相关差异，且该反应主要由大鼠微粒体乙醇氧化酶的主要酶——属于3A亚家族的P450酶催化。
