Screening for Serotonin Receptor 4 Agonists Using a GPCR-Based Sensor in Yeast.

More than 30% of all pharmaceuticals target G-protein-coupled receptors (GPCRs). Here, we present a GPCR-based screen in yeast to identify ligands for human serotonin receptor 4 (5-HTR ₄ ). Serotonin receptor 4 agonists are used for the treatment of irritable bowel syndrome with constipation. Specifically, the HTR ₄ -based screen couples activation of 5-HTR ₄ on the yeast cell surface to luciferase reporter expression. The HTR ₄ -based screen has a throughput of one compound per second allowing the screening of more than a thousand compounds per day.