Prostaglandin E2 (PGE2) production pathway (PGE2 pathway)

The Prostaglandin E2 (PGE2) production pathway is a critical enzymatic sequence responsible for generating PGE2, one of the most abundant and biologically active lipid mediators in the human body [1: StatPearls, NSAIDs]. The pathway initiates with the release of arachidonic acid from cell membranes by phospholipase A2, followed by its conversion into the intermediate prostaglandin H2 (PGH2) by the bifunctional enzymes cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) [2: PubMed, PMID 15554159]. PGH2 is subsequently isomerized into PGE2 by specific prostaglandin E synthases, most notably the inducible microsomal PGES-1 (mPGES-1), which is often upregulated during inflammatory responses [3: PubMed, PMID 17170604]. PGE2 exerts its effects by binding to four distinct G protein-coupled receptors (EP1-EP4), influencing diverse processes such as pain sensitization, fever, vasodilation, and gastric mucosal protection [4: JBC, 2007]. Clinically, this pathway is the primary target for nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors, which alleviate symptoms by reducing PGE2 levels [5: Am J Med, 1998]. However, because PGE2 is also essential for maintaining physiological homeostasis in the stomach and kidneys, systemic inhibition of this pathway can lead to adverse effects like gastrointestinal ulcers and renal impairment [6: J Pharm Pharm Sci, 2013].

Other names

Arachidonic acid cascade (PGE2 branch)Prostanoid biosynthesis pathwayCOX-PGES pathwayCyclooxygenase pathway

Inhibition of cyclooxygenase (COX-1 and COX-2) enzymes to prevent the conversion of arachidonic acid into prostaglandin H2, thereby blocking the downstream synthesis of prostaglandin E2 [1: StatPearls].