Involvement of CYP2C in the metabolism of cannabinoids by human hepatic microsomes from an old woman.
The hepatic microsomal metabolism of cannabinoids was studied using the liver from an old woman. delta 8-Tetrahydrocannabinol, delta 9-tetrahydrocannabinol and cannabinol were biotransformed to their respective 11-hydroxy metabolites by a microsomal fraction with specific activities (pmol/min/mg protein) of 29.1, 47.1 and 27.9, respectively. In addition, both 11-oxo-delta 8-tetrahydrocannabinol and 11-oxo-delta 9-tetrahydrocannabinol were metabolized to the corresponding carboxylic acids with the microsomes. An antibody against mouse CYP2C29 almost completely inhibited 11-hydroxylation of the cannabinoids and microsomal aldehyde oxygenase (MALDO) activity for 11-oxo-delta 8-tetrahydrocannabinol and 11-oxo-delta 9-tetrahydrocannabinol, used as substrates, whereas an antibody against rat CYP3A2 conversely stimulated the 11-hydroxylation of delta 8-tetrahydrocannabinol and MALDO activity for 11-oxo-delta 8-tetrahydrocannabinol. The results indicate that a member of CYP2C is primarily responsible for the metabolism of the above cannabinoids in the human hepatic microsomes.
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
K
K
Watanabe
T
T
Matsunaga
I
I
Yamamoto
Y
Y
Funae
H
H
Yoshimura
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D002186:Cannabinoids / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D006801:Humans; D006900:Hydroxylation; D008565:Membrane Proteins; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology*; D051381:Rats; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000378:metabolism*
D002186:Cannabinoids; D008565:Membrane Proteins; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C465260:Cyp3a2 protein, rat; D051544:Cytochrome P-450 CYP3A; D039181:Steroid 16-alpha-Hydroxylase