Prostaglandin E2, a member of the autacoid family of lipid mediators, is a major renal cyclooxygenase product of arachidonic acid metabolism. Prostaglandin E2 binds to four G protein-coupled E-prostanoid receptors, designated EP1, EP2, EP3 and EP4. The expression and function of the prostaglandin E2 receptors have been highly characterized in kidney. EP1, which is predominantly expressed in the collecting duct, couples to Gq proteins to inhibit sodium absorption and increase in intracellular calcium, which act as second messengers. EP2 is coupled to Gs proteins, which stimulate adenylyl cyclase.EP2 has the lowest expression in kidney, but EP2 knockout mice exhibit saltsensitive hypertension, which suggests a role for EP2 in salt excretion. EP3, which is expressed in renal vessels, thick ascending limb and collecting duct, has at least six alternative splice variants that couple to Gi proteins to inhibit cAMP, which subsequently inhibit sodium and water transport. In uterus, EP3 induces the contraction of uterine smooth muscles. EP4 is expressed in glomerulus and collecting duct. It couples to Gs proteins, which stimulate adenylyl cyclase and regulate glomerular tone and renal renin release.