Prostaglandin E2 receptor 2 and 4 (EP2 and EP4) (EP2/EP4)

Prostanoid EP2 and EP4 receptors are G protein-coupled receptors that mediate the signaling of Prostaglandin E2 (PGE2), a key lipid mediator in inflammation and cancer. Both receptors primarily couple to the Gs protein, leading to the activation of adenylate cyclase and an increase in intracellular cyclic AMP (cAMP) (UniProt P43116, P35408). In the tumor microenvironment, PGE2 acts through EP2 and EP4 to create an immunosuppressive milieu by inhibiting the activity of cytotoxic T cells and natural killer cells while promoting the expansion of regulatory T cells and myeloid-derived suppressor cells (PubMed: 30104348). Because of this role, EP2 and EP4 are major targets in immuno-oncology, where antagonists are used to restore the immune system's ability to attack tumors. Beyond cancer, these receptors are involved in regulating vascular tone, gastrointestinal mucosal protection, and bone metabolism (PubMed: 28254954). Therapeutic strategies include the development of selective antagonists for cancer and agonists for treating conditions like glaucoma or promoting bone healing. However, targeting these receptors requires careful management of potential side effects related to their broad physiological roles in the renal and gastrointestinal systems.

Other names

PTGER2PTGER4Prostanoid EP2 receptorProstanoid EP4 receptorPGE2 receptor 2PGE2 receptor 4Prostaglandin E2 receptor subtype EP2Prostaglandin E2 receptor subtype EP4

Antagonism of EP2 and EP4 receptors to inhibit PGE2-mediated immunosuppression and tumor growth; Agonism to stimulate bone formation or reduce intraocular pressure.