Prostaglandin E₂ inhibits renal collecting duct Na⁺ absorption by activating the EP₁ receptor

PGE₂ exerts potent diuretic and natriuretic effects on the kidney. This action is mediated in part by direct inhibition of collecting duct Na⁺ absorption via a Ca⁺⁺-coupled mechanism. These studies examine the role the Ca⁺⁺-coupled PGE-E EP₁ receptor plays in mediating these effects of PGE₂ on Na⁺ transport. Rabbit EP₁ receptor cDNA was amplified from rabbit kidney RNA. Nuclease protection assays demonstrated highest expression of EP₁ mRNA in kidney, followed by stomach, adrenal, and ileum. In situ hybridization, demonstrated renal expression of EP₁ mRNA was exclusively over the collecting duct. In fura-2-loaded microperfused rabbit cortical collecting duct, EP₁ active PGE analogs were 10-1,000-fold more potent in raising intracellular Ca⁺⁺ than EP₂, EP₃, or EP₄-selective compounds. Two different EP₁ antagonists, AH6809 and SC19220, completely blocked the PGE₂- stimulated intracellular calcium increase. AH6809 also completely blocked the inhibitory effect of PGE₂ on Na⁺ absorption in microperfused rabbit corticol collecting ducts. These studies suggest that EP₁ receptor activation mediates PGE₂-dependent inhibition of Na⁺ absorption in the collecting duct, thereby contributing to its natriuretic effects.