FIGURE 1.

An overview of PG biosynthesis, receptors, and downstream signalling pathways. Arachidonic acid (AA) is released from membrane phospholipids via the actions of cytosolic PLA₂ (cPLA₂) following various stimuli and then metabolised to PGH₂ by COXs (COX‐1 and COX‐2). PGH₂ is unstable and subsequently converted into PGs, that is, PGD₂, PGE₂, PGF_2α, PGI₂, and TXA₂ by the actions of their synthases PGDS (LPGDS and HPGDS), PGES (mPGES‐1, mPGES‐2, and cPGES), PGFS (AKR1B1 and PGFS/ABR1C3), PGIS, and TXAS, respectively. PGs bind to their receptors and activate different downstream signalling pathways. PGD₂ receptors, DP1 and DP2, activate the cAMP and PI3K pathways, respectively, while DP2 also represses the cAMP pathway. PGE₂ receptors EP2 and EP4 activate both cAMP and PI3K pathways, EP1 activates PKC and Ca²⁺ pathways, and EP3 deactivates the cAMP pathway. Both PGF_2α receptor FP and TXA₂ receptor TP activate PKC and Ca²⁺ pathways, whereas PGI₂ receptor IP triggers activation of cAMP signalling. On the other hand, non‐steroidal anti‐inflammatory drugs (NSAIDs) inhibit AA biosynthesis of all PGs by targeting COX‐1 and/or COX‐2