The G-protein-coupled receptor (GPCR) superfamily represents one of the most important classes of drug targets. GPCRs are divided into subfamilies according to the kind of Gα protein to which they couple. There are Gαs-, Gαi-, and Gαq-coupled receptors. Gαs proteins can activate adenyl cyclase and increase the intracellular concentration of cAMP. Here we employ both 3xCRE element and firefly luciferase as reporters to establish host cell lines that can be used for research involving GPCRs, particularly Gs-coupled GPCRs. The cell line demonstrates an approximately 30-fold dynamic range in the luciferase assay, providing a good screening window that is suitable for screening of GPCR agonist and antagonist.