Figure 1.

PGE2 synthesis and signaling pathways. Arachidonic acid (AA) is liberated from membrane phospholipids by catalysis of phospholipase A2 (PLA2), subsequently converted into PGH2 via COXs including COX-1 and COX-2. NSAIDs can restrain COX activity. Synthesized by PGE synthase (cPGES, mPGES-1, and mPGES-2), PGE2 exerts its effects by binding to G protein-coupled receptors EP1-EP4. Both activated EP1 (coupled to Gq) and EP3 (coupled with Gi) could increase intracellular Ca²⁺ via phospholipase C (PLC). Activated EP3 receptors could inhibit cAMP production via adenylate cyclase (AC). Activated EP2 or EP4 (both coupled to Gs) could elevate cAMP production via AC. Arrowheads refer to stimulation, whereas blunt ends indicate inhibition.