PGE2

Prostaglandin E2 (PGE2) is a lipid mediator in the prostanoid family, derived from arachidonic acid. It is produced by cells through the cyclooxygenase (COX) pathway: arachidonic acid is released by phospholipase A2, converted by COX-1 and COX-2 to PGH2, and then isomerized by PGE synthases to PGE2. PGE2 is among the most abundant prostaglandins produced at sites of inflammation and in many tissues.

Functional effects are mediated by four G protein–coupled receptors, EP1–EP4, with tissue-specific signaling. EP1 typically signals via Gq to raise intracellular calcium; EP2 and EP4 activate adenylate cyclase and raise cAMP; EP3 signals through Gi (and other pathways) to lower cAMP. Consequently, PGE2 has diverse actions including pyretic and nociceptive effects, vasodilation, increased vascular permeability, bronchoconstriction or relaxation depending on context, and modulation of renal, gastrointestinal, and reproductive physiology.

Physiological and clinical relevance: PGE2 contributes to fever and pain sensitization during inflammation, regulates renal blood flow and salt handling, protects gastric mucosa but can promote mucus production and secretion. In the reproductive system, PGE2 promotes cervical ripening and uterine contractions at term. In tumors, PGE2 often promotes angiogenesis, immune suppression, and tumor progression; COX-2–driven PGE2 production is a feature of several cancers.

Clinical implications: Nonsteroidal anti-inflammatory drugs (NSAIDs) block COX enzymes, reducing PGE2 synthesis and providing analgesic and anti-inflammatory effects; side effects include gastric injury and renal effects. Misoprostol, a PGE1 analog, is used to prevent NSAID-induced ulcers. Dinoprostone (PGE2) is used clinically to induce labor and to promote cervical ripening; it has also been used in obstetric procedures.