EP4

EP4, or prostaglandin E receptor 4, is a member of the EP receptor family that binds prostaglandin E2 (PGE2). In humans, EP4 is encoded by the PTGER4 gene and is expressed in many tissues including immune cells, the nervous system, bone, and the gastrointestinal tract. As a G protein-coupled receptor, EP4 mediates cellular responses to PGE2 and participates in the regulation of inflammation and pain.

Signaling: EP4 primarily couples to Gs proteins, leading to increased intracellular cyclic AMP, activation of protein kinase A and EPAC, and downstream transcriptional effects. In some contexts, β-arrestin–dependent signaling contributes to EP4 responses. Receptor activity can be modulated by receptor internalization, desensitization, and cross-talk with other prostaglandin receptors.

Physiological and pathological roles: EP4 signaling modulates fever and pain, influences immune cell function, and participates in bone remodeling and tissue repair. In cancer, EP4 activation can promote tumor growth and metastasis, making EP4 a target of interest in oncology research and therapy development.

Therapeutic relevance: EP4 antagonists are being explored to treat inflammatory diseases and cancer. Grapiprant is a selective EP4 antagonist used in veterinary medicine for osteoarthritis in dogs; other EP4 antagonists are under investigation in human trials for pain, inflammatory diseases, and cancer. Potential effects reflect the broader role of prostaglandin signaling in gastrointestinal, renal, and vascular systems.

Note: EP4 may also denote Episode 4 in various media franchises; this article focuses on the prostaglandin receptor.