Differential localization of prostaglandin E receptor subtypes in human kidney

Four prostaglandin E(2) (PGE(2)) receptors designated EP(1), EP(2), EP(3), and EP(4) have been pharmacologically identified, cloned, and sequenced. The present studies determined the intrarenal distribution of these EP-receptor subtypes in human kidney using in situ hybridization with riboprobes for the human EP receptors. mRNA for the phosphatidylinositol hydrolysis-coupled EP(1) receptor was highly expressed in cortical, outer medullary, and inner medullary collecting duct. RNA for the G(i)-coupled EP(3) receptor was primarily expressed in the cortical and outer medullary collecting duct, as well as in the medullary thick ascending limb; however, it was absent from the inner medullary collecting duct. Expression of mRNA for EP(1) and EP(3) in connecting segment could not be excluded. There was no expression of the G(s)-coupled EP(2) receptor mRNA detected in human kidney by in situ hybridization; however, mRNA for the G(s)-coupled EP(4) receptor was highly expressed in the glomerulus. These studies demonstrate distinct regions of intrarenal expression for the different EP receptors and suggest that each receptor subtype may modulate different aspects of renal function in humans.