treatment of certain diseases. There are several such agonists including butaprost free acid and ONO-AE1-259-01 which have Ki inhibitory binding values (see Biochemistry#Receptor/ligand binding affinity) of 32 and 1.8 NM, respectively, and therefore are respectively ~2.5-fold less and 7-fold more potent than PGE2. Inhibiting ligands PF-04418948 (Ki=16 nM), TG4-155 (Ki=9.9 nM), TG8-4, and TG6-129 are selective competitive antagonists for EP2 that have been used for studies in animal models of human diseases. Many of the earlier EP2 receptor antagonists used for such studies exhibited poor receptor selectivity, inhibiting, for example, other EP receptors. Mechanism of cell activation EP2 is classified as a relaxant type of prostanoid receptor based on its ability, upon activation, to relax certain types of smooth muscle (see Prostaglandin receptors). When initially bound to PGE2 or any other of its agonists, it mobilizes G proteins containing the Gs alpha subunit (i.e. Gαs)-G beta-gamma complexes (i.e. Gβγ). The Gαs- Gβγ complexes dissociate into their Gαs and Gβγ subunits which in turn regulate cell signaling pathways. In particular, Gαs stimulates adenylyl cyclase to raise cellular levels of cAMP thereby activating PKA; PKA activates various types of signaling molecules such as the transcription factor CREB which lead to different types of functional responses depending on cell type. EP2 also activates the a) GSK-3 pathway which regulates cell migratory responses and innate immune responses including pro-inflammatory cytokine and interleukin production and b) Beta-catenin pathway which regulates not only cell–cell adhesion but also activates the Wnt signaling pathway which, in turn, stimulates the transcription of genes responsible for regulating cell migration and proliferation. In many of these respects, EP2 actions resemble those of another type of relaxant prostanoid receptor, EP4 but differs from the contractile prostanoid receptors, EP1 and EP3 receptors which mobilize G proteins containing the Gαq-Gβγ complex. EP2 also differs from all the other prostaglandin receptors in that it fails to undergo homologous desensitization. That is, following agonist-induced activation, the other prostaglandin (as well as most types of G protein coupled receptors) quickly become desensitized, often internalized, and whether or not internalized, incapable of activating their G protein targets. This effect limits the duration and extent to which agonists can stimulate cells. EP2, by failing to become desensitized, is able to function over prolong periods and later time points than other prostaglandin receptors and therefore potentially able to contribute to more delayed and chronic phases of cellular and tissue responses.