Induction of microsomal prostaglandin E2 synthase in the macula densa in children with hypokalemic salt-losing tubulopathies.
In hyperprostaglandin E syndrome (HPGES) and classic Bartter syndrome (cBS), tubular salt and water losses stimulate renin secretion, which is dependent on enhanced cyclooxygenase-2 (COX-2) enzymatic activity. In contrast to other renal COX metabolites, only prostaglandin E(2) (PGE(2)) is selectively up-regulated in these patients. To determine the intrarenal source of PGE(2) synthesis, we analyzed the expression of microsomal PGE(2) synthase (mPGES; EC: 5.3.99.3), whose product PGE(2) has been shown to stimulate renin secretion in vitro. Expression of mPGES was analyzed by immunohistochemistry in eight patients with HPGES, in two patients with cBS, and in six control subjects. Expression of mPGES immunoreactive protein was observed in cells of the macula densa in five of eight HPGES patients and in one of two cBS patients. Expression of mPGES immunoreactive protein was not observed in cells associated with the macula densa in kidneys from control subjects without a history consistent with activation of the renin angiotensin system. Co-induction of COX-2 and mPGES in cells of the macula densa suggests that PGE(2) activates renin secretion in humans.
Kömhoff
Martin
M
Department of Pediatrics, Philipps-University, Deutschhausstrasse 12, D-35033 Marburg, Germany. koemhoff@med.uni-marburg.de
Reinalter
Stephan C
SC
Gröne
Hermann J
HJ
Seyberth
Hannsjörg W
HW
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000293:Adolescent; D000918:Antibody Specificity; D002648:Child; D002675:Child, Preschool; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000652:urine; D005260:Female; D006801:Humans; D007008:Hypokalemia / Q000378:metabolism*; D007150:Immunohistochemistry; D019746:Intramolecular Oxidoreductases / Q000276:immunology / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism; D007606:Juxtaglomerular Apparatus / Q000201:enzymology*; D007674:Kidney Diseases / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D008861:Microsomes / Q000201:enzymology; D000071876:Prostaglandin-E Synthases; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012083:Renin / Q000378:metabolism; D012492:Salts / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D007527:Isoenzymes; D008565:Membrane Proteins; D012492:Salts; D015121:6-Ketoprostaglandin F1 alpha; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D012083:Renin; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone