Immunolocalization of the four prostaglandin E-2 receptor proteins EP1, EP2, EP3, and EP4 in human kidney

Four prostaglandin E-2 receptor subtypes designated EP1, EP2, EP3, and EP4 have been shown to mediate a variety of effects of prostaglandin E-2 (PGE(2 )) on glomerular hemodynamics, tubular salt and water reabsorption, and on blood vessels in the human kidney. Despite the important role of renal PGE, , the localization of PGE(2) receptor proteins in the human kidney is unkno wn. The present study used antipeptide antibodies to the EP1 to EP4 recepto r proteins for immunolocalization in human kidney tissue. Immunoblot studie s using these antibodies demonstrated distinct bands in membrane fraction f rom human kidney. By means of immunohistochemistry, expression of the human EP1 receptor subtype protein in renal tissue was detected mainly in connec ting segments, cortical and medullary collecting ducts, and in the media of arteries and afferent and efferent arterioles. The human EP2 receptor subt ype protein was detectable only in the media of arteries and arterioles. Th e human EP3 receptor subtype protein was strongly expressed in glomeruli, T amm-Horsfall negative late distal convoluted tubules, connecting segments, cortical and medullary collecting ducts, as well as in the media and the en dothelial cells of arteries and arterioles. Staining of the human EP4 recep tor subtype protein was observed in glomeruli and in the media of arteries. However, no signal of either receptor subtype was detected in the thick as cending limb, the macula densa, or in adjacent juxtaglomerular cells. These results support the concept that PGE(2) modulates specific functions in di fferent anatomical structures of the human kidney.