Cytochrome P-450 isozymes involved in the oxidative metabolism of Δ9-tetrahydrocannabinol by liver microsomes of adult female rats

S. Narimatsu, K. Watanabe, T. Matsunaga, I. Yamamoto, S. Imaoka, Y. Funae, H. Yoshimura

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)79-83
Number of pages5
JournalDrug Metabolism and Disposition
Volume20
Issue number1
Publication statusPublished - Jan 1 1992

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Fingerprint Dive into the research topics of 'Cytochrome P-450 isozymes involved in the oxidative metabolism of Δ<sup>9</sup>-tetrahydrocannabinol by liver microsomes of adult female rats'. Together they form a unique fingerprint.

  • Cite this

    Narimatsu, S., Watanabe, K., Matsunaga, T., Yamamoto, I., Imaoka, S., Funae, Y., & Yoshimura, H. (1992). Cytochrome P-450 isozymes involved in the oxidative metabolism of Δ9-tetrahydrocannabinol by liver microsomes of adult female rats. Drug Metabolism and Disposition, 20(1), 79-83.