Prostaglandin E2 receptor 3 (EP3) (EP3)

The Prostaglandin E2 receptor 3 (EP3) is a G protein-coupled receptor (GPCR) encoded by the PTGER3 gene that serves as a high-affinity receptor for prostaglandin E2 (PGE2) (UniProt P43115). It is characterized by significant structural diversity due to extensive alternative splicing of its C-terminal tail, allowing it to couple with multiple G proteins including Gi, Gs, and Gq to elicit varied cellular responses (IUPHAR/BPS Guide to Pharmacology). Biologically, EP3 is a key mediator of the febrile response in the hypothalamus, an inhibitor of gastric acid secretion in the stomach, and a potent inducer of smooth muscle contraction in the uterus and vasculature (PubMed PMID: 9634236). In the pancreas, EP3 signaling has been linked to the inhibition of insulin secretion, making it a target of interest for type 2 diabetes research (PubMed PMID: 24509544). Pharmacologically, EP3 agonists like misoprostol are used clinically for gastric protection and labor induction, while selective antagonists are being explored for treating cardiovascular disorders and overactive bladder (ClinicalTrials.gov). However, therapeutic use is often limited by side effects such as gastrointestinal distress and the risk of unintended uterine contractions in pregnant patients (FDA Misoprostol Label).

Other names

PTGER3Prostanoid EP3 receptorPGE receptor EP3 subtypeProstaglandin E receptor 3

Agonism of the EP3 receptor typically results in the inhibition of adenylate cyclase via Gi proteins, leading to decreased intracellular cAMP levels, or the activation of phospholipase C via Gq proteins, increasing intracellular calcium (UniProt P43115; IUPHAR/BPS Guide to Pharmacology).