Non-invasive Profiling of Endogenous G Protein-Coupled Receptors in Living Cells with Optical Biosensors
作者单位：Coming Inc
会议名称：《第十五届国际药理学大会》
会议日期：2006年
学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学]
摘 要：正 Dynamic redistribution of cellular contents, equivalent to dynamic mass redistribution （DMR）. is common to many cellular processes including the signaling through G protein- coupled receptors （GPCRs） in response to stimulation. The DMR can be manifested by resonant waveguide grating （RWG） biosensors,and the resultant DMR signal offers a novel and integrated readout for sensing living cells under real physiological conditions. Upon investigating the DMR signals of quiescent A431 cells mediated trough the activation of endogenous GPCRs using the RWG biosensors in combination with a panel of GPCR agonists, a unique DMR sinature was identified for each class of GPCRs. based on the G protein（s） with which the receptor is coupled （i.e.. Gq. Gs and Gi）. The DMR signals were dependent on the doses of agonists and the expression levels of endogenous receptors. The dose - dependent switching from one type of DMR signal to another was observed for a small set of GPCR agonists. Together with its ability to screen GPCR modulators using endpoint measurements, the labelfree and noninvasivebiosensors hold great potentials for GPCR drug discovery and deorphanization.