具有偏向性的大麻素受体配体研究进展

Advances in the Research on Biased Ligands of Cannabinoid Receptors

大麻素受体是多种疾病的潜在治疗靶标,属于G蛋白偶联受体(GPCR)的A家族,主要包括大麻素Ⅰ型受体(CB1)和大麻素Ⅱ型受体(CB2),分布在体内不同部位。现有研究多集中于2种亚型受体的选择性而非具体信号通路的选择性,但已有研究显示信号通路的选择性与成瘾性密切相关。受体激活后,CB1和CB2与下游每个信号传导途径的作用程度不同,该现象称为偏向性激动。GPCR与配体结合时的构象是多样化的,偏向性激动剂选择性地稳定一组受体构象,特定地激活下游信号传导途径,从而降低不良反应。综述大麻素受体的结构特征、偏向性信号以及偏向性配体的研究进展,以期为相关研究提供参考。

Cannabinoid receptors,class A family of G protein-coupled receptors(GPCR)that have been proposed as potential therapeutic targets for varieties of diseases,have two main subtypes,CB1 and CB2,which are expressed in different tissues and organs.Most existing studies have been focused on the selectivity of the two subtypes of receptors rather than that of the specific signal pathways,but it has been found that drug addiction is related to the selectivity of signal pathways.Activation of CB1 and CB2 receptors leads to different effects on each downstream signal transduction pathway,which is called biased agonism.GPCRs show multiple conformations when bound with different agonists,and biased agonists can selectively stabilize a subset of conformations and activate a specific downstream signaling pathway,thereby reducing side effects.This paper focuses on the structural characteristics of cannabinoid receptors,biased signals and research advances of biased ligands,in order to provide reference for related research.