Prostaglandin E2 (PGE2) gastric cytoprotection pathway

The gastric mucosal prostaglandin E2 (PGE2) synthesis and mucus production pathway is a fundamental physiological mechanism for protecting the stomach lining from autodigestion. PGE2 is synthesized from arachidonic acid primarily by the constitutive enzyme cyclooxygenase-1 (COX-1) in the gastric mucosa (Source: Physiological Reviews). Once synthesized, PGE2 acts on E-prostanoid receptors, particularly the EP3 and EP4 subtypes, to stimulate the secretion of a protective layer of mucus and bicarbonate ions, which neutralize gastric acid and provide a physical barrier (Source: StatPearls). This pathway also regulates mucosal blood flow and inhibits acid secretion from parietal cells, further maintaining mucosal integrity (Source: Journal of Gastroenterology). The pathway is a major site of drug interaction; non-steroidal anti-inflammatory drugs (NSAIDs) inhibit PGE2 synthesis, which can lead to gastric erosions and peptic ulcers. Conversely, synthetic prostaglandin analogs like misoprostol and cytoprotective agents like rebamipide are used to enhance this pathway and prevent mucosal injury (Source: PubChem).

Other names

Gastric mucosal barrierPGE2-mediated cytoprotectionGastric mucus-bicarbonate barrierGastric mucosal PGE2 synthesis

Drugs targeting this pathway either inhibit the synthesis of PGE2 (NSAIDs), leading to mucosal damage, or act as PGE2 analogs (misoprostol) and synthesis stimulators (rebamipide) to enhance mucus and bicarbonate production and provide cytoprotection.