Prostaglandin E receptor 4 (EP4)

The Prostaglandin E receptor 4 (EP4) is a G protein-coupled receptor that serves as a primary mediator for the biological actions of Prostaglandin E2 (PGE2) (UniProt P35408). Upon activation, EP4 primarily couples with Gs proteins to stimulate adenylate cyclase, leading to an increase in intracellular cyclic AMP (cAMP) levels and the activation of downstream pathways like PKA and PI3K (IUPHAR/BPS Guide to Pharmacology). It is widely expressed across various tissues, including the immune system, vascular smooth muscle, and the gastrointestinal tract, where it regulates functions such as T-cell differentiation, vasodilation, and mucosal protection (PMID: 25633141). In the context of disease, EP4 is frequently upregulated in various cancers, where it promotes an immunosuppressive tumor microenvironment by inhibiting the activity of cytotoxic T cells and natural killer cells while promoting the expansion of myeloid-derived suppressor cells (PMID: 28811310). Consequently, EP4 has emerged as a significant therapeutic target; EP4 antagonists are being investigated in clinical trials to enhance the efficacy of cancer immunotherapies, while EP4 agonists are explored for their potential in treating inflammatory bowel disease and promoting bone healing (Frontiers in Pharmacology, 2017). Grapiprant is a notable EP4 antagonist currently utilized in veterinary medicine for the management of osteoarthritis pain (Journal of Veterinary Internal Medicine, 2016).

Other names

PTGER4Prostanoid EP4 receptorPGE receptor EP4 subtypeProstaglandin E2 receptor EP4 subtype

Agonists bind to the receptor to activate Gs proteins, increasing intracellular cAMP levels; Antagonists competitively inhibit the binding of PGE2 to prevent downstream signaling and immunosuppression.