Effects of two cannabinoids on hepatic microsomal cytochrome P-450

K. Watanabe, K. Hamajima, S. Narimatsu, I. Yamamoto, H. Yoshimura

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The effects of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (Δ9-THC) on the synthesis and degradation of hepatic microsomal cytochrome P-450 were studied in mice. Cannabinoids used (10, 50 and 100 mg/kg, i.p.) did not affect δ-aminolevulinic acid synthetase activity in the liver. Δ9-THC-treatment (10, 50 and 100 mg/kg, i.p.) markedly stimulated heme oxygenase activity in hepatic 18000 x g supernatant fractions in a dosedependent manner, whereas CBD-treatment was without effect. In vitro experiments, CBD and Δ9-THC (40 to 160 μM) markedly inhibited nicotinamide adenine dinucleotide phosphate (NADPH)-induced lipid peroxidation in hepatic microsomes. When CBD was incubated with the hepatic microsomes in the presence of an NADPH-generating system, cytochrome P-450 content decreased significantly. However, Δ9-THC showed no effects in similar experiments. The rate of decrease in the cytochrome P-450 content using CBD (160 μM) was 0.212 nmol/mg protein/20 min in microsomes from control mice. This value increased significantly in microsomes from phenobarbital-treated mice (0.792 nmol/mg protein/20 min) but not in those from 3-methylcholanthrene-treated mice (0.190 nmol/mg protein/20 min). The metabolic rate (per nmol cytochrome P-450) of CBD was also increased significantly by phenobarbital-treatment but not by 3-methylcholanthrene-treatment. These results suggest that CBD metabolites rather than CBD itself, play some role in the decreasing effect on cytochrome P-450 content in the hepatic microsomes in vitro, and that the microsomal formation of reactive metabolite of CBD is increased by phenobarbital-treatment.

Original languageEnglish
Pages (from-to)39-45
Number of pages7
JournalJournal of Pharmacobio-Dynamics
Volume9
Issue number1
Publication statusPublished - 1986
Externally publishedYes

Fingerprint

Cannabidiol
Cannabinoids
Cytochrome P-450 Enzyme System
Microsomes
Liver
Dronabinol
Phenobarbital
Methylcholanthrene
NADP
5-Aminolevulinate Synthetase
Heme Oxygenase (Decyclizing)
Proteins
Lipid Peroxidation

ASJC Scopus subject areas

  • Pharmacology

Cite this

Watanabe, K., Hamajima, K., Narimatsu, S., Yamamoto, I., & Yoshimura, H. (1986). Effects of two cannabinoids on hepatic microsomal cytochrome P-450. Journal of Pharmacobio-Dynamics, 9(1), 39-45.

Effects of two cannabinoids on hepatic microsomal cytochrome P-450. / Watanabe, K.; Hamajima, K.; Narimatsu, S.; Yamamoto, I.; Yoshimura, H.

In: Journal of Pharmacobio-Dynamics, Vol. 9, No. 1, 1986, p. 39-45.

Research output: Contribution to journalArticle

Watanabe, K, Hamajima, K, Narimatsu, S, Yamamoto, I & Yoshimura, H 1986, 'Effects of two cannabinoids on hepatic microsomal cytochrome P-450', Journal of Pharmacobio-Dynamics, vol. 9, no. 1, pp. 39-45.
Watanabe K, Hamajima K, Narimatsu S, Yamamoto I, Yoshimura H. Effects of two cannabinoids on hepatic microsomal cytochrome P-450. Journal of Pharmacobio-Dynamics. 1986;9(1):39-45.
Watanabe, K. ; Hamajima, K. ; Narimatsu, S. ; Yamamoto, I. ; Yoshimura, H. / Effects of two cannabinoids on hepatic microsomal cytochrome P-450. In: Journal of Pharmacobio-Dynamics. 1986 ; Vol. 9, No. 1. pp. 39-45.
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