G蛋白偶联受体
脱敏(药物)
受体
逮捕
兴奋剂
背景(考古学)
细胞生物学
生物
视紫红质样受体
药理学
化学
生物化学
代谢受体
古生物学
作者
Chengchun Min,Xiaohan Zhang,Mei Zheng,Ningning Sun,Srijan Acharya,Xiaowei Zhang,Kyeong-Man Kim
出处
期刊:Biomolecules & Therapeutics
[The Korean Society of Applied Pharmacology]
日期:2017-05-01
卷期号:25 (3): 239-248
被引量:9
标识
DOI:10.4062/biomolther.2016.193
摘要
Desensitization and acute tolerance are terms used to describe the attenuation of receptor responsiveness by prolonged or intermittent exposure to an agonist.Unlike desensitization of G protein-coupled receptors (GPCRs), which is commonly explained by steric hindrance caused by the b-arrestins that are translocated to the activated receptors, molecular mechanisms involved in the acute tolerance of GPCRs remain unclear.Our studies with several GPCRs and related mutants showed that the acute tolerance of GPCRs could occur independently of agonist-induced b-arrestin translocation.A series of co-immunoprecipitation experiments revealed a correlation between receptor tolerance and interactions among receptors, b-arrestin2, and Gbg.Gbg displayed a stable interaction with receptors and b-arrestin2 in cells expressing GPCRs that were prone to undergo tolerance compared to the GPCRs that were resistant to acute tolerance.Strengthening the interaction between Gbg and b-arrestin rendered the GPCRs to acquire the tendency of acute tolerance.Overall, stable interaction between the receptor and Gbg complex is required for the formation of a complex with b-arrestin, and determines the potential of a particular GPCR to undergo acute tolerance.Rather than turning off the signal, b-arrestins seem to contribute on continuous signaling when they are in the context of complex with receptor and Gbg.
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