| Scientific Background: | Prostaglandin E2 (PGE2) is an extensively studied prostaglandin owing to its predominance in inflammation, cancer, atherosclerosis, autoimmune disease, and sepsis. Oxidation of arachidonic acid by prostaglandin synthases (COX-1 and COX-2) produces prostaglandin H2 (PGH2), which is further metabolized by PGE synthases into its major product, PGE2. PGE2 mediates autocrine and paracrine signaling by binding to G-protein coupled receptors (EP1, EP2, EP3, EP4) on the cell surface, functioning to modulate phospholipase C and adenylate cyclase activity. PGE2 has been of great interest as a therapeutic target, either by modulation of its synthesis by COX inhibitors (NSAIDS) or by modulation of its receptors by downregulation or binding antagonists. PGE2 production in a variety of tissues has been shown to modulate numerous physiological processes including natriuresis in the kidney, smooth muscle elasticity in the vasculature, and the inflammatory response to damaged tissues by monocytes and macrophages. |
