Prostaglandin E receptor 3 (EP3) (EP3)

Prostaglandin E receptor 3 (EP3) is a G protein-coupled receptor (GPCR) that serves as one of the four primary receptors for prostaglandin E2 (PGE2) [1, 6]. It is uniquely characterized by its multiple isoforms generated through alternative splicing, which allow it to couple with various G proteins, most notably Gαi to inhibit adenylate cyclase and decrease intracellular cAMP levels [1, 7, 10]. EP3 is widely expressed across tissues, including the gastrointestinal tract, kidneys, brain, and vasculature, where it regulates critical processes such as gastric acid secretion, fever induction, and smooth muscle contraction [1, 2, 3, 9]. In the cardiovascular system, EP3 activation on platelets promotes aggregation, making it a target for anti-thrombotic drug development [1, 5, 15]. Clinically, EP3 agonists like misoprostol are utilized for gastric mucosal protection and labor induction, while selective antagonists are being investigated for treating thrombosis and inflammatory conditions [1, 3, 5, 13]. The receptor also plays a significant role in cancer progression and immune modulation, with its expression often serving as a prognostic marker in certain malignancies [2, 9, 15]. However, therapeutic targeting of EP3 must account for potential safety concerns, such as gastrointestinal side effects and the risk of inducing uterine contractions in pregnant patients [1, 3, 5].

Other names

Prostanoid E receptor 3PTGER3PGE2 receptor EP3 subtypePGE receptor EP3 subtypeProstanoid EP3 receptorEP3 receptor

EP3 agonists bind to the receptor and primarily couple with Gαi proteins to inhibit adenylate cyclase, leading to decreased intracellular cAMP levels [1, 3, 10]. Depending on the isoform, the receptor can also couple with Gαq or Gα12/13 to increase intracellular calcium and activate Rho-mediated pathways [7, 12]. These signaling events mediate physiological effects such as the inhibition of gastric acid secretion, induction of uterine contractions, and enhancement of platelet aggregation [1, 2, 15]. Antagonists selectively block these pathways, particularly to inhibit platelet activation and prevent thrombosis [1, 5, 15].