Vasudevan Neelakantan T
Thermalin Inc., Cleveland, OH, United States.
Methods Cell Biol. 2017;142:51-57. doi: 10.1016/bs.mcb.2017.07.014. Epub 2017 Sep 23.
GPCRs are a major family of cell surface receptors and the most druggable protein targets in modern medicine. Recent elucidation of crystal structures of a vast number of GPCRs eludes to the finer details of biased agonism or functional selectivity of many of these receptors and warrants a better understanding of their biological effects as well as therapeutic potential. Receptor function is measured in terms desensitization/resensitization, which provides insights on receptor activation and differential coupling to various G proteins. This review article presents thoughts on the potential of GPCR desensitization assay/cAMP assay, a highly sensitive and versatile platform for high-throughput assays for elucidating novel functions of many orphan GPCRs. Besides, these assays also are very sensitive to screen for agonists, partial agonists, or antagonists and provide a simplified system for novel drug discovery for Gs-coupled GPCRs and understanding their physiological implications.
G蛋白偶联受体（GPCRs）是细胞表面受体的一个主要家族，也是现代医学中最具药物开发潜力的蛋白质靶点。最近，大量GPCRs晶体结构的阐明揭示了许多此类受体偏向激动或功能选择性的更细微细节，这就需要更好地了解它们的生物学效应以及治疗潜力。受体功能通过脱敏/再敏化来衡量，这为受体激活以及与各种G蛋白的差异偶联提供了见解。这篇综述文章探讨了GPCR脱敏测定/cAMP测定的潜力，这是一个用于高通量测定的高度灵敏且通用的平台，可用于阐明许多孤儿GPCRs的新功能。此外，这些测定对于筛选激动剂、部分激动剂或拮抗剂也非常敏感，并为Gs偶联GPCRs的新药发现提供了一个简化系统，同时有助于理解它们的生理意义。
