Prostaglandin E2 receptor (EP2 and EP3) (EP2 and EP3)

Prostaglandin E2 (PGE2) receptors, specifically the EP2 and EP3 subtypes, are G protein-coupled receptors (GPCRs) that mediate the diverse physiological and pathological effects of PGE2, a key lipid mediator derived from arachidonic acid (nih.gov). The EP2 receptor (PTGER2) primarily couples to Gs proteins, leading to increased intracellular cAMP levels, and is involved in processes such as ovulation, bone formation, and bronchodilation (wikipedia.org). In disease states, EP2 signaling often promotes chronic inflammation, neurodegeneration, and tumor progression, making it a target for both agonists, such as omidenepag isopropyl for glaucoma, and antagonists for cancer or epilepsy (acs.org). The EP3 receptor (PTGER3) is unique for its multiple splice variants and primarily couples to Gi proteins to inhibit cAMP production, though it can also signal through Gq and G12/13 (nih.gov). EP3 is critical for fever generation, gastric mucosal protection, and uterine contraction; its agonists like misoprostol are clinically used for labor induction and ulcer prevention (wikipedia.org). Targeting these receptors offers a more specific therapeutic approach than broad COX inhibition, potentially avoiding the cardiovascular and gastrointestinal side effects associated with non-steroidal anti-inflammatory drugs (NSAIDs) (nih.gov).

Other names

PTGER2PTGER3EP2EP3Prostanoid EP2 receptorProstanoid EP3 receptorPGE2 receptorProstaglandin E receptor 2Prostaglandin E receptor 3

EP2 agonists activate Gs-coupled signaling to increase cAMP, promoting vasodilation and bone healing; EP2 antagonists block these pathways to reduce neuroinflammation and tumor growth. EP3 agonists primarily activate Gi-coupled signaling to decrease cAMP, inducing uterine contraction and inhibiting gastric acid secretion, while also potentially signaling through Gq and G12/13 pathways.