人源大麻素受体的结构生物学研究

doi:10.3969/j.issn.0253-9608.2021.01.004

摘要/Abstract

摘要： 据史料记载，早在公元200年前中国已将大麻（cannabis）用于镇痛及其他疾病的治疗，随后人们在娱乐和宗教活动中也开始使用大麻。随着科学技术的不断进步，大麻中的多种活性成分被逐步鉴定出来，其中就包含具有精神活性的四氢大麻酚（Δ9 -tetrahydrocannabinol, Δ9 -THC）。这些活性成分是一类结构和功能多样的化学物质，统称为大麻素（cannabinoid）。20世纪90年代初期，科学家们发现人体和一些动物体内存在一类内源性大麻素系统，该系统参与调控体内的多种生理过程，其中包含内源性大麻素和大麻素受体（cannabinoid receptor）。目前人体中已知的大麻素受体属于G蛋白偶联受体（G protein coupled receptor, GPCR），主要包含大麻素受体亚型I（cannabinoid receptor type 1, CB1）和大麻素受体亚型II（cannabinoid receptor type 2, CB2），其中CB1主要分布在中枢神经系统，而CB2在外周免疫系统中高量表达。它们介导的信号通路与多种疾病密切相关，是非常重要的药物靶标。大麻素主要包括植物性大麻素（phytocannabinoids）、内源性大麻素（endocannabinoids）和合成型大麻素（synthetic cannabinoids）等三大类。文章回顾了大麻及大麻素的历史，总结了大麻素受体CB1和CB2的结构与功能研究进展，以及它们在学习与认知、情绪、肥胖、疼痛及免疫等相关疾病治疗中的应用前景。

关键词: 大麻, 大麻素, 大麻素受体, 三维结构

Abstract: Marijuana from Cannabis sativa L. has been used for both therapeutic and recreational purpose for many centuries. Δ9 - tetrahydrocannabinol (Δ9 -THC), the main psychoactive constituent of marijuana, was discovered and isolated in 1964. In the early 1990s, the endocannabinoid system was identified in mammalian species. The cannabinoids from marijuana and endocannabinoids exert their effects mainly through the cannabinoid receptors CB1 and CB2, which belong to the G protein-coupled receptors (GPCRs). CB1 is highly expressed in the central nervous system, while CB2 is widely distributed in the immune system. CB1 and CB2 can regulate a variety of central and peripheral physiological processes and are very important drug targets for treating diverse diseases. Here, we briefly summarized the history of cannabinoids and the progress in the structural and functional studies of CB1 and CB2, and discussed their therapeutic potentials in learning, mood, obesity, pain and inflammation.

沈灵, 华甜, 刘志杰. 人源大麻素受体的结构生物学研究[J]. 自然杂志, 2021, 43(1): 25-31.

SHEN Ling, HUA Tian, LIU Zhijie. Structural studies of human cannabinoid receptors [J]. Chinese Journal of Nature, 2021, 43(1): 25-31.

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