Oxidation of 7-Hydroxy-Δ8-tetrahydrocannabinol to 7-Oxo-Δ8-tetrahydrocannabinol
Abstract
The oxidative activities of 7α- and 7β-hydroxy-Δ8-tetrahydrocannabinol (7α- and 7β-hydroxy-Δ8-THC) to 7-oxo-Δ8-THC in hepatic microsomes of mice were significantly increased by the treatment of mice with dexamethasone or phenobarbital. A cytochrome P450 enzyme, named P450MDX-B, was purified from hepatic microsomes of dexamethasone-treated mice, and its apparent molecular mass was estimated to be 51,000. The NH2-terminal amino acid sequence of P450MDX-B was the same as that of CYP3A11. The oxidative activities of 7α- and 7β-hydroxy-Δ8-THC were 2.55 and 4.92 nmol/min/nmol P450, respectively. The antibody against P450MDX-B almost completely inhibited the oxidative activities of 7α- and 7β-hydroxy-Δ8-THC in mice. These results indicate that P450MDX-B (CYP3A11) is a major enzyme responsible for the oxidation of 7α- and 7β-hydroxy-Δ8-THC to 7-oxo-Δ8-THC in mouse liver.
Footnotes
-
Send reprint requests to: Dr. Ikuo Yamamoto, Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa 920-1181, Japan.
-
This work was partially supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan, and by the Special Research Fund of Hokuriku University.
- Abbreviations used are::
- THC
- tetrahydrocannabinol
- MALCO
- microsomal alcohol oxygenase
- P450
- cytochrome P450
- HPLC
- high-performance liquid chromatography
- Received January 27, 1998.
- Accepted May 27, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
DMD articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|
