Prostaglandin is a small molecule produced from arachidonic acid by the enzymes COX1, COX2 and PG synthase. PGE2 regulates various factors of inflammatory response, promoting local vasodilatation and attracting immune system cells to the site of the inflammation.

Prostanoid EP3 receptor, a member of the G-protein coupled receptor superfamily, is one of four PGE2 receptors (EP1-EP4) and binds PGE2 with a higher affinity than other receptors of its class. Unlike EP2 and EP4, EP3 is not coupled to G_s and lacks cAMP activating functions. In contrast, most of its splice variants couple with G_i and inhibit adenylate cyclase activity¹. EP3 binds prostaglandin in a GTP dependent manner. One of the receptor’s extracellular domains, ECII, can alter GTP effect on agonist binding and thus the receptor’s downstream intracellular signaling. ECII causes receptor conformational changes².

EP3 plays a role in pulmonary hypertension (PAH) pathophysiology. It is hypothesized that EP3 levels are upregulated in pulmonary arterial smooth muscle cells and in human distal pulmonary arteries in response to hypoxia. Blocking agents for the EP3 receptor may prove as a useful strategy in the treatment of PAH³.

EP3 is also involved in the cell growth, invasion and migration of many tumor types including bladder cancer. EP3 has been found to be significantly less expressed in muscular and non-muscular invasive bladder cells than in normal urothelial cells⁴.