Figure 1.

Arachidonic acid (AA) is liberated from the plasma membrane via phospholipase A2 (PLA2). AA can be recycled by the Lands cycle, which is a reacylation/deacylation cycle, that serves to keep the concentration of free AA at a low level. AA is converted by cyclooxygenase 1 or 2 (COX-1/COX-2) to PGH₂ which is then converted to PGE₂, PGF_2α, PGD₂, PGI₂, or TXA₂ by prostaglandin specific synthases. PGE₂ is exported out of the cell by multidrug resistance-associated protein four (MRP4) where it can bind to its receptors, the E series of prostaglandin receptors on the plasma membrane, EP1-4. Each of the G-protein-coupled- receptors signal through a different intracellular pathway: EP1 leads to elevation of intracellular calcium through Gαq, EP3, which exists in multiple isoforms, can lead to different responses with the majority acting to inhibit cAMP through Gαi as well as an increase in IP3/intracellular calcium; EP2 and EP4 cause stimulation of cyclic AMP (cAMP) production and protein kinase A (PKA) by sequential activation of Gαs and adenylate cyclase (AC); EP4 can also activate phosphoinositide-3-kinase (PI3K) through Gαi. PGE₂ is imported back into the cell through prostaglandin transporter (PGT) where it can either be re-exported or inactivated by 15-hydroxyprostaglandin dehydrogenase (15-PGDH) to 15-keto-PGE₂. 15-keto-PGE₂ can signal through PPARγ. PGE₂ can be converted to PGA₂ through a dehydration reaction. PGD₂ through a series of dehydrogenation reactions creates PGJ₂, delta-12-prostaglandin J2 (d-12-PGJ₂) and 15-deoxy-delta12,14-prostaglandin J2 (15-d-PGJ₂). PGI₂ can either signal through PPARδ intracellularly or exported via multidrug resistance protein (MRP) to signal through the IP receptor. TXA₂ is exported out of the cell via MRP to signal through the TP receptor. PGF_2α is exported out of the cell via MRP where it can signal via the FP receptor on the cell surface.