G protein-coupled receptors (GPCRs) are essential for cellular responses to external stimuli, by triggering changes in cyclic AMP (cAMP) pathways and the phosphatidylinositol pathway. Near half of the current drugs target GPCRs signaling.
Anne Marie Quinn, founder of Montana Molecular, explains on SelectScience how it’s possible to measure, in real time, multiple signaling pathways inside a living cell.
“Our very first product was for detection of diacylglycerol (DAG) an important component of GPCR signaling through the Gq pathway. We specifically wanted to differentiate between Gs, Gi and Gq signaling,” notes Quinn. “This is an important goal for both drug discovery and basic research.”
“Upon ligand binding, the Gs-coupled GPCR receptor activates adenylyl cyclase that in turn produces cAMP, governing important cellular responses. Gi-coupled GPCR receptors, however, inhibit adenylyl cyclase and cAMP production. The phosphatidylinositol pathway, on the other hand, is triggered by the Gq-coupled receptors. In Gq-coupled signaling, DAG and intracellular calcium act as second messengers, ultimately influencing cell functions.”
The fluorescent bioscensors developped by Montana Molecular allow to follow both intracellular cAMP and DAG.
The use of two biosensors measuring different players in cell signaling can reveal more about the effects of a drug. Image courtesy of Montana Molecular for SelectScience
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