Oxidative metabolism of Δ9-tetrahydrocannabinol (THC) by liver microsomes was studied in female rats. Δ9-THC was mainly biotransformed to 11-hydroxy-Δ9-THC (11-OH-Δ9-THC) and 9α, 10α-epoxy-hexahydrocannabinol (EHHC) by liver microsomal fraction of adult female rat. Two isozymes of cytochrome P-450 (P-450) [F-1 (IIC6) and F-2 (IIC12)] were purified from liver microsomes of female rats and oxidation activities toward Δ9-THC were assessed in the reconstituted system containing NADPH-P-450 reductase and cytochrome b5. P-450 F-1 showed considerable activity toward 11-OH-Δ9-THC formation (10.62 nmol/min/nmol of P-450), whereas P-450 F-2 did not show any activity toward Δ9-THC oxidation under the conditions used. Preincubation of microsomes with antiserum against P-450 F-1 obtained from rabbits caused a marked decrease in 11-OH-Δ9-THC formation, whereas antiserum against P-450 F-2 did not exhibit any inhibitory effect on the oxidation of Δ9-THC by liver microsomes of adult female rats. Further, antiserum against P-450 F-1 or F-2 did not affect the microsomal formation of 9α, 10α-EHHC from Δ9-THC. These results indicate that P-450 F-1 and its immunochemically related P-450 isozyme(s) play important roles in the formation of an active metabolite, 11-OH-Δ9-THC, from Δ9-THC by liver microsomes of adult female rats.
|Number of pages||5|
|Journal||Drug Metabolism and Disposition|
|Publication status||Published - Jan 1 1992|
ASJC Scopus subject areas
- Pharmaceutical Science