cAMP assays in GPCR drug discovery.

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.