Abstract
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 E2 (PGE2) is selectively up-regulated in these patients. To determine the intrarenal source of PGE2 synthesis, we analyzed the expression of microsomal PGE2 synthase (mPGES; EC: 5.3.99.3), whose product PGE2 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 PGE2 activates renin secretion in humans.
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Abbreviations
- cBS:
-
classic Bartter syndrome
- COX:
-
cyclooxygenase
- HPGES:
-
hyperprostaglandin e syndrome
- mPGES:
-
microsomal prostaglandin E2 synthase
- PG:
-
prostaglandin
- RAS:
-
renin-angiotensin system
- SLT:
-
salt-losing tubulopathy
- TAL:
-
thick ascending limb of Henle's loop
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Acknowledgements
We thank Matthew D. Breyer for providing pCDNA3.1mPGES expression vector and control tissue and Claudia Schmidt for excellent technical assistance.
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Supported by Stiftung P. E. Kempkes, Marburg (19-2000 & 26-2001) and Deutsche Forschungsgemeinschaft (KO 1855/2-1) to M.K.
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Kömhoff, M., Reinalter, S., Gröne, H. et al. Induction of Microsomal Prostaglandin E2 Synthase in the Macula Densa in Children with Hypokalemic Salt-Losing Tubulopathies. Pediatr Res 55, 261–266 (2004). https://doi.org/10.1203/01.PDR.0000101747.09626.6B
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DOI: https://doi.org/10.1203/01.PDR.0000101747.09626.6B
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