Induction of Microsomal Prostaglandin E2 Synthase in the Macula Densa in Children with Hypokalemic Salt-Losing Tubulopathies

Autor: Martin Kömhoff, Stephan C. Reinalter, Hermann Josef Gröne, Hannsjörg W. Seyberth
Rok vydání: 2004
Předmět:
Zdroj: Pediatric Research. 55:261-266
ISSN: 1530-0447
0031-3998
DOI: 10.1203/01.pdr.0000101747.09626.6b
Popis: 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.
Databáze: OpenAIRE