Characterization of microsomal alcohol oxygenase catalyzing the oxidation of 7-hydroxy-Δ8-tetrahydrocannabinol to 7-oxo-Δ8- tetrahydrocannabinol in rat liver

Tamihide Matsunaga; Kinya Shibayama; Shinsuke Higuchi; Hiroyuki Tanaka; Kazuhito Watanabe; Ikuo Yamamoto

doi:10.1248/bpb.23.43

Characterization of microsomal alcohol oxygenase catalyzing the oxidation of 7-hydroxy-Δ⁸-tetrahydrocannabinol to 7-oxo-Δ⁸- tetrahydrocannabinol in rat liver

Tamihide Matsunaga, Kinya Shibayama, Shinsuke Higuchi, Hiroyuki Tanaka, Kazuhito Watanabe, Ikuo Yamamoto

Pharmaceutical Health Care and Sciences

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

Abstract

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 oxidation of 7-hydroxy-Δ⁸-THC to 7-oxo-Δ⁸-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.

Original language	English
Pages (from-to)	43-46
Number of pages	4
Journal	Biological and Pharmaceutical Bulletin
Volume	23
Issue number	1
DOIs	https://doi.org/10.1248/bpb.23.43
Publication status	Published - Jan 2000

All Science Journal Classification (ASJC) codes

Pharmacology
Pharmaceutical Science

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Characterization of microsomal alcohol oxygenase catalyzing the oxidation of 7-hydroxy-Δ⁸-tetrahydrocannabinol to 7-oxo-Δ⁸- tetrahydrocannabinol in rat liver. / Matsunaga, Tamihide; Shibayama, Kinya; Higuchi, Shinsuke; Tanaka, Hiroyuki; Watanabe, Kazuhito; Yamamoto, Ikuo.

In: Biological and Pharmaceutical Bulletin, Vol. 23, No. 1, 01.2000, p. 43-46.

Research output: Contribution to journal › Article › peer-review

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abstract = "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 oxidation of 7-hydroxy-Δ8-THC to 7-oxo-Δ8-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.",

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