Prostanoids are a series of arachidonic acid metabolites produced by the action of cyclooxygenase and subsequently by isomerases and synthases. Cells rapidly secrete prostanoids after synthesis, whereupon the prostanoids bind to a family of 8 GPCRs to exert their biological effects (Narumiya and FitzGerald, 2001). The prostaglandin PGE2 causes pain, vasodilation, immunosuppression of T cells, bone resorption and promotion of carcinogenesis. Four related GPCRs, EP1, EP2, EP3 and EP4, each bind to PGE2, but the different G protein coupling status of each receptor leads to distinct biological effects; EP1 couples primarily to Gq to mobilize intracellular calcium. EP1 appears to mediate the effects of PGE2 in promoting formation of precancerous lesions in animal models of colon cancer (Watanabe et al., 1999). In addition, EP1 has an inhibitory effect on stress-induced aggressive and risk-taking behaviors in mice (Matsuoka et al., 2005). The cloned human EP1-expressing cell line is made in the Chem-1 host, which supports high levels of recombinant EP1 expression on the cell surface and contains high levels of the promiscuous G protein Gα15 to enhance coupling of the receptor to the calcium signaling pathway. Thus, the cell line is an ideal tool for screening for antagonists of interactions between EP1 and its ligands.