TY - JOUR
T1 - Cytochrome P-450 isozymes involved in the oxidative metabolism of Δ9-tetrahydrocannabinol by liver microsomes of adult female rats
AU - Narimatsu, S.
AU - Watanabe, K.
AU - Matsunaga, T.
AU - Yamamoto, I.
AU - Imaoka, S.
AU - Funae, Y.
AU - Yoshimura, H.
PY - 1992/1/1
Y1 - 1992/1/1
N2 - 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.
AB - 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.
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M3 - Article
C2 - 1347001
AN - SCOPUS:0026594950
SN - 0090-9556
VL - 20
SP - 79
EP - 83
JO - Drug Metabolism and Disposition
JF - Drug Metabolism and Disposition
IS - 1
ER -