Department of Veterans Affairs Medical Center and Vanderbilt University, Division of Nephrology, Departments of Medicine, Pharmacology, and Molecular Physiology and Biophysics, Nashville, Tennessee, USA, Department of Physiology and Medicine, University of Ottawa, Ottawa, Ontario, Canada

Correspondence: Matthew D. Breyer, M.D., S-3223 MCN, Vanderbilt University Medical Center, 1161 21st Avenue South, Nashville, Tennessee 37232-2372, USA. E-mail: Matthew.Breyer@mcmail.vanderbilt.edu

Abstract

Regulation of renal function by prostaglandin E receptors. Prostaglandin E₂ is the major cyclooxygenase product of arachidonic acid metabolism produced along the nephron. This autacoid interacts with four distinct, G-protein—coupled E-prostanoid receptors designated EP₁—EP₄. The intrarenal distribution of each receptor has been mapped and the consequences of receptor activation examined. EP₃ receptor mRNA is expressed highly in the medullary thick ascending limb (mTAL) and collecting duct (CD). EP₃ receptor activation inhibits cAMP generation via G_i, thus inhibiting vasopressin-stimulated water reabsorption in the CD. EP₃ receptor activation also may contribute to PGE₂-mediated inhibition of NaCl absorption in the mTAL. The EP₁ receptor is coupled to increased cell [Ca²⁺]. EP₁ mRNA expression is restricted to the CD, and receptor activation inhibits Na⁺ absorption. PGE₂ also increases cAMP generation in the cortical thick ascending limb and CD; this may be due to EP₄ receptor activation. EP₄ mRNA is readily detected in the CD with little detectable EP₂ expression. The EP₄ receptor appears to be expressed both on luminal and basolateral membranes. EP₄ receptor activation also may contribute to the regulation of renin release by the juxtaglomerular apparatus. The consequences of renal EP-receptor activation for salt and water balance may be determined by the relative renal expression of each of these receptors.