EFFECTS OF TWO CANNABINOIDS ON HEPATIC MICROSOMAL CYTOCHROME P-450
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概要
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The effects of cannabidiol (CBD) and Δ^9-tetrahydrocannabinol (Δ^9-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. Δ^9-THC-treatment (10,50 and 100 mg/kg, i.p. ) markedly stimulated heme oxygenase activity in hepatic 18000 ×g supernatant fractions in a dose-dependent manner, whereas CBD-treatment was without effect. In vitro experiments, CBD and Δ^9-THC (40 to 160μM) 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, Δ^9-THC showed no effects in similar experiments. The rate of decrease in the cytochrome P-450 content using CBD (160μM) 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.
- 社団法人日本薬学会の論文
著者
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中村 紳一郎
Specialty Chemicals Research Center Shin-etsu Chemical Co. Ltd.
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YOSHIMURA HIDETOSHI
Faculty of Pharmaceutical Sciences, Kyushu University
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YAMAMOTO Ikuo
School of Pharmaceutical Sciences, Kyushu University of Health and Welfare
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Yamamoto Ikuo
北陸大学 薬 衛化
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Nakamura S
Specialty Chemicals Research Center Shin-etsu Chemical Co. Ltd.
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WATANABE KAZUHITO
School of Pharmacy, Hokuriku University
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NARIMATSU SHIZUO
School of Pharmacy, Hokuriku University
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HAMAJIMA KOICHI
School of Pharmacy, Hokuriku University, Kanazawa
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Nakamura Satoko
Osaka University Of Pharmaceutical Sciences
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Yoshimura Hidetoshi
Faculty Of Pharmaceutical Sciences Kyushu University
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Hamajima Koichi
School Of Pharmacy Hokuriku University
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Watanabe Kazuhito
Faculty Of Pharmaceutical Sciences Kyushu University
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Yamamoto Ikuo
School Of Pharmaceutical Sciences Kyushu University Of Health And Welfare
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