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, PGF2α 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.