Prostaglandin E receptors and the kidney

Prostaglandin E-2 is a major renal cyclooxygenase metabolite of arachidonat e and interacts with four G protein-coupled E-prostanoid receptors designat ed EP1, EP2, EP3, and EP4. Through these receptors, PGE(2) modulates renal hemodynamics and salt and water excretion. The intrarenal distribution and function of EP receptors have been partially characterized, and each recept or has a distinct role. EP1 expression predominates in the collecting duct where it inhibits Na+ absorption, contributing to natriuresis. The EP2 rece ptor regulates vascular reactivity, and EP2 receptor-knockout mice have sal t-sensitive hypertension. The EP3 receptor is also expressed in vessels as well as in the thick ascending limb and collecting duct, where it antagoniz es vasopressin-stimulated salt and water transport. EP4 mRNA is expressed i n the glomerulus and collecting duct and may regulate glomerular tone and r enal renin release. The capacity of PGE(2) to bidirectionally modulate vasc ular tone and epithelial transport via constrictor EP1 and EP3 receptors vs . dilator EP2 and EP4 receptors allows PGE(2) to serve as a buffer, prevent ing excessive responses to physiological perturbations.