阿片受体泛素化机制及其对受体功能的影响  

Mechanism of opioid receptor ubiquitination and its effect on receptor function

作　　者：江洁冰 周培岚[2] 郑志兵[1,2] 苏瑞斌[1,2] 

机构地区：[1]广西医科大学药学院,广西南宁530021 [2]军事医学科学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：《中国药理学与毒理学杂志》2015年第2期302-309,共8页Chinese Journal of Pharmacology and Toxicology

基　　金：国家自然科学基金(81473194);国家自然科学基金(30901799);北京市自然科学基金(7092078);国家科技重大专项(2012ZX09301003-003)~~

摘　　要：阿片受体是一类重要的G蛋白偶联受体(GPCR),是内源性阿片肽及阿片类药物结合的靶点,阿片受体激活后对神经系统、免疫及内分泌系统具有调节作用。但阿片受体在反复激活后,容易出现耐受,导致阿片成瘾。受体的内吞和再循环对受体复敏具有重要意义。近年来研究发现,受体的泛素化修饰参与了GPCR的转运过程,并且多数配体作用于阿片受体后,受体的泛素化水平明显升高。将阿片受体的泛素化位点突变后,对不同阿片受体亚型的内吞和降解过程产生了不同的影响,进而影响了阿片受体的信号转导过程。本文着重对阿片受体3种亚型的泛素化修饰特点及泛素化对受体转运的调节作用进行综述。Opioid receptors, as an important member of G protein coupled receptors （GPCR）, are the binding targets of endogenous opioid peptides and exogenous opiates. The activation of opioid receptors influences the nervous system, immune physiology and endocrine system. However, prolonged activation of opioid receptors is likely to produce opioid tolerance, leading to opioid addiction. Receptor endocytosis and sorting into the recycling pathway contribute to recovery of cellular opioid responsiveness. Recent studies have revealed that GPCR can be modulated by ubiquitination which plays a unique roles in governing GPCR trafficking. Moreover, ubiquitination of the opioid receptors （μ, κand δ） is increased after stimulation of most opioid agonists. Mutation of the ubiquitin sites affects the internalization and degradation of opioid receptors, which contributes to changes in signal pathways and regulation of opioid receptors. ln this paper, ubiquitination of opioid receptors and the fundamental role of ubiquitination in trafficking of opioid receptors are reviewed.

关 键 词：G蛋白偶联受体 泛素化 阿片受体 溶酶体 

分 类 号：R96[医药卫生—药理学]