Prostaglandin receptors in the kidney: a new route for intervention?

Prostaglandins comprise a structurally diverse family of cyclooxygenase metabolites of arachidonic acid, including thromboxane A2, PGD2, PGE2, PGF2alpha and PGI2. These prostaglandins are now known to act via different G-protein-coupled receptors. PGE2, the major prostaglandin synthesized along the nephron, interacts with at least four E-prostanoid (EP) receptors, three of which are highly expressed in distinct regions of the kidney. Each EP receptor also preferentially couples to a different signal transduction pathway, including stimulation of cAMP generation by the EP2 and EP4 receptors; inhibition of cAMP generation, via Gi by EP3 receptors, and activation of phosphatidylinositol hydrolysis by EP1 receptor. Other intrarenal prostanoid receptors include the thromboxane A2 receptor and the prostacyclin receptor. These receptors also exhibit a discrete intrarenal distribution. The possibility of pharmacologically targeting each renal prostanoid receptor may provide a unique approach to modifying renal function in disease states.