Prostaglandin E receptor 3 isoform 4 (EP3-IV) (EP3-IV)

Prostaglandin E receptor 3 (PTGER3), specifically the splice variant IV, is a G protein-coupled receptor (GPCR) that serves as a high-affinity receptor for Prostaglandin E2 (PGE2) (UniProt P43115). This receptor is notable for its extensive C-terminal alternative splicing, which allows for diverse G-protein coupling and varying levels of constitutive activity (PubMed: 8316106). Isoform IV is particularly distinct because it can couple to multiple G-proteins, including Gi, Gs, and G12/13, thereby influencing adenylate cyclase activity and Rho-mediated pathways (IUPHAR/BPS Guide to Pharmacology). It is involved in a wide range of physiological functions such as inhibiting gastric acid secretion, modulating neurotransmitter release, and regulating smooth muscle tone in the vasculature and airways (PubMed: 7534331). In clinical contexts, PTGER3 is a target for drugs like misoprostol, used for gastric protection and labor induction, and is implicated in conditions like inflammatory pain and cardiovascular disorders (PubChem CID 5282387). Research into isoform-specific signaling is crucial for developing selective therapies that can target specific pathological processes without broad systemic side effects.

Other names

PTGER3 splice variant IVEP3-4Prostanoid EP3 receptor isoform 4PGE receptor EP3 subtype isoform 4PTGER3 isoform d

Agonists bind to the receptor to activate G-protein signaling pathways (primarily Gi, but also Gs or G12/13 for this specific isoform), leading to the modulation of second messengers like cAMP and calcium, while antagonists block these interactions to prevent pathological signaling.