致幻剂激活5-HT_(2A)R产生致幻作用的信号通路研究进展  

Advances in signaling pathway of 5-HT_(2A) receptor activation induced by psychedelics

作　　者：朱慧丽 周培岚 傅风华[1] 苏瑞斌 ZHU Hui-li;ZHOU Pei-lan;FU Feng-hua;SU Rui-bin(School of Pharmacy,Yantai University,Yantai,Shandong 264005,China;State Key Laboratory of Toxicology and Medical Countermeasures,Institute of Pharmacology and Toxicology,Academy of Military Medical Sciences,Beijing 100850,China)

机构地区：[1]烟台大学药学院,山东烟台264005 [2]军事科学院军事医学研究院毒物药物研究所,抗毒药物与毒理学国家重点实验室,北京100850

出　　处：《中国药理学通报》2022年第11期1607-1612,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金面上项目(No81773709)。

摘　　要：经典血清素能致幻剂(又称致幻剂)是一种强大的精神活性物质可以强烈改变人的知觉、情绪和认知。目前普遍认为,致幻剂发挥致幻作用的主要靶点为5-HT_(2A)受体(5-hydroxytryptamine 2A Receptor,5-HT_(2A) R)。研究发现,5-HT_(2A) R作为G蛋白偶联受体,除了偶联经典的Gα_(q/11)-PLCβ信号通路外,还可偶联Gα_(i/o)、Gα_(12/13)和β-arrestin2等信号通路。但是,与致幻作用相关的受体后信号通路尚无定论。该文总结了近年来致幻剂激活5-HT_(2A) R后产生致幻作用的信号通路研究进展,为阐明幻觉产生的分子机制及发现新的药物靶点提供依据。Classic serotonergic hallucinogens(also known as psychedelics)are powerful psychoactive substances that can induce profound alterations of human consciousness,emotion,and cognition.It is generally believed that the main target of psychedelics for their hallucinogenic effect is 5-hydroxytryptamine 2A receptor(5-HT_(2A) R).As the G protein-coupled receptor,5-HT_(2A) R can couple Gα_(i/o),Gα_(12/13) andβ-arrestin2 signaling pathways in addition to the classical Gα_(q/11)-PLC_(β) signaling pathway.However,the post-receptor signaling pathways involved in hallucinogenic effects have not been demonstrated.This paper summarizes the recent research progress on the signaling pathway of hallucinogenic effects after 5-HT_(2A) R activation,and also demonstrates the molecular mechanism of hallucinations for discovering new drug targets.

关 键 词：致幻剂 G蛋白偶联受体 5-HT_(2A)受体 信号转导 偏向性 G蛋白 β-arrestin2 

分 类 号：R341[医药卫生—基础医学] R392.11R964R971.4