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Immunolocalization of a microsomal prostaglandin E synthase in rabbit kidney

Nephrology Research and Training Center, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294

Submitted 19 December 2002 ; accepted in final form 9 May 2003

PGE₂, the major cyclooxygenase (COX) metabolite of arachidonic acid, is an important paracrine regulator of numerous tubular and vascular functions in the kidney. To date, COX activity has been considered the key step in prostaglandin synthesis and is well characterized. However, much less is known about the recently cloned microsomal PGE₂ synthase (mPGES), the terminal enzyme of PGE₂ synthesis, which converts COX-derived PGH₂ to the biologically important PGE₂. Present studies provide the detailed localization of mPGES protein in the rabbit kidney using immunohistochemistry. In the cortex, strong mPGES labeling was found in the macula densa (MD) and principal cells of the connecting segment and cortical collecting tubule but not in intercalated cells. The medulla was abundant in mPGES-positive structures, with heavy labeling in the collecting duct system. In descending thin limbs and renal medullary interstitial cells, mPGES expression was less intense, and it was below the limits of detection in the vasa recta. Expression of MD mPGES, similarly to COX-2, was greatly increased in response to low-salt diet and angiotensin I-converting enzyme inhibition by captopril. These findings suggest autocrine regulation of renal salt and water transport by PGE₂ in descending thin limb and collecting tubule and a paracrine effect of PGE₂ on the glomerular and medullary vasculature. Similar to other organs, mPGES in the kidney is an inducible enzyme and may be similarly regulated and acts in concert with COX-2.

membrane-associated prostaglandin E synthase; cyclooxygenase-2; macula densa; collecting duct; principal cells; descending thin limb; immunohistochemistry

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