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1 Division of Nephrology and Departments of Medicine, 2 Molecular Physiology and Biophysics, and 3 Pharmacology, Veterans Affairs Medical Center and Vanderbilt University School of Medicine, Nashville, Tennessee 37232
Prostaglandin E2 is a major renal cyclooxygenase metabolite of arachidonate and interacts with four G protein-coupled E-prostanoid receptors designated EP1, EP2, EP3, and EP4. Through these receptors, PGE2 modulates renal hemodynamics and salt and water excretion. The intrarenal distribution and function of EP receptors have been partially characterized, and each receptor has a distinct role. EP1 expression predominates in the collecting duct where it inhibits Na+ absorption, contributing to natriuresis. The EP2 receptor regulates vascular reactivity, and EP2 receptor-knockout mice have salt-sensitive hypertension. The EP3 receptor is also expressed in vessels as well as in the thick ascending limb and collecting duct, where it antagonizes vasopressin-stimulated salt and water transport. EP4 mRNA is expressed in the glomerulus and collecting duct and may regulate glomerular tone and renal renin release. The capacity of PGE2 to bidirectionally modulate vascular tone and epithelial transport via constrictor EP1 and EP3 receptors vs. dilator EP2 and EP4 receptors allows PGE2 to serve as a buffer, preventing excessive responses to physiological perturbations.
prostaglandin E2 transport; hemodynamics; sodium; water
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