Involvement of CYP2C in the metabolism of cannabinoids by human hepatic microsomes from an old woman.
Involvement of CYP2C in the metabolism of cannabinoids by human hepatic microsomes from an old woman.
复制标题
CYP2C 参与老妇人肝微粒体的大麻素代谢。
DOI：
10.1248/bpb.18.1138
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发表时间：
1995
影响因子：
2
通讯作者：
H. Yoshimura
中科院分区：
文献类型：
--
作者：
Kazuhito Watanabe;T. Matsunaga;I. Yamamoto;Y. Funae;H. Yoshimura
大麻素的肝微粒体代谢进行了研究，使用肝脏从一个老妇人。δ 8-四氢大麻酚、δ 9-四氢大麻酚和大麻酚被微粒体部分生物转化为它们各自的11-羟基代谢物，其比活性（pmol/min/mg蛋白质）分别为29.1、47.1和27.9。此外，11-氧代-δ 8-四氢大麻酚和11-氧代-δ 9-四氢大麻酚均被微粒体代谢为相应的羧酸。针对小鼠CYP 2C 29的抗体几乎完全抑制大麻素的11-羟基化以及用作底物的11-氧代-δ 8-四氢大麻酚和11-氧代-δ 9-四氢大麻酚的微粒体醛加氧酶（MALDO）活性，而针对大鼠CYP 3A 2的抗体相反地刺激δ 8-四氢大麻酚的11-羟基化以及11-氧代-δ 8-四氢大麻酚的MALDO活性。结果表明，CYP 2C的一个成员主要负责上述大麻素在人肝微粒体中的代谢。
The hepatic microsomal metabolism of cannabinoids was studied using the liver from an old woman. delta 8-Tetrahydrocannabinol, delta 9-tetrahydrocannabinol and cannabinol were biotransformed to their respective 11-hydroxy metabolites by a microsomal fraction with specific activities (pmol/min/mg protein) of 29.1, 47.1 and 27.9, respectively. In addition, both 11-oxo-delta 8-tetrahydrocannabinol and 11-oxo-delta 9-tetrahydrocannabinol were metabolized to the corresponding carboxylic acids with the microsomes. An antibody against mouse CYP2C29 almost completely inhibited 11-hydroxylation of the cannabinoids and microsomal aldehyde oxygenase (MALDO) activity for 11-oxo-delta 8-tetrahydrocannabinol and 11-oxo-delta 9-tetrahydrocannabinol, used as substrates, whereas an antibody against rat CYP3A2 conversely stimulated the 11-hydroxylation of delta 8-tetrahydrocannabinol and MALDO activity for 11-oxo-delta 8-tetrahydrocannabinol. The results indicate that a member of CYP2C is primarily responsible for the metabolism of the above cannabinoids in the human hepatic microsomes.