Abstract | AIM: METHODS: Activation of amiloride-sensitive currents by uPA and plg were studied in Xenopus laevis oocytes expressing murine ENaC. In doxorubicin-induced nephrotic mice, uPA was inhibited pharmacologically by amiloride and genetically by the use of uPA-deficient mice (uPA-/- ). RESULTS: Experiments in Xenopus laevis oocytes expressing murine ENaC confirmed proteolytic ENaC activation by a combination of plg and uPA which stimulated amiloride-sensitive currents with concomitant cleavage of the ENaC γ-subunit at the cell surface. Treatment of nephrotic wild-type mice with amiloride inhibited urinary uPA activity, prevented urinary plasmin formation and sodium retention. In nephrotic mice lacking uPA (uPA-/- ), urinary plasmin formation from plg was suppressed and urinary uPA activity absent. However, in nephrotic uPA-/- mice, sodium retention was not reduced compared to nephrotic uPA+/+ mice. Amiloride prevented sodium retention in nephrotic uPA-/- mice which confirmed the critical role of ENaC in sodium retention. CONCLUSION:
|
Authors | Bernhard N Bohnert, Sophie Daiminger, Matthias Wörn, Florian Sure, Tobias Staudner, Alexandr V Ilyaskin, Firas Batbouta, Andrea Janessa, Jonas C Schneider, Daniel Essigke, Sandip Kanse, Silke Haerteis, Christoph Korbmacher, Ferruh Artunc |
Journal | Acta physiologica (Oxford, England)
(Acta Physiol (Oxf))
Vol. 227
Issue 4
Pg. e13286
(12 2019)
ISSN: 1748-1716 [Electronic] England |
PMID | 31006168
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | © 2019 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd. |
Chemical References |
- Epithelial Sodium Channel Blockers
- Epithelial Sodium Channels
- Amiloride
- Sodium
- Urokinase-Type Plasminogen Activator
|
Topics |
- Amiloride
(administration & dosage, pharmacology)
- Animals
- Dose-Response Relationship, Drug
- Epithelial Sodium Channel Blockers
(administration & dosage, pharmacology)
- Epithelial Sodium Channels
(genetics, metabolism)
- Gene Expression Regulation
(drug effects)
- Ion Channel Gating
- Mice
- Mice, Knockout
- Nephrotic Syndrome
- Oocytes
- Sodium
(metabolism)
- Urokinase-Type Plasminogen Activator
(genetics, metabolism)
- Xenopus laevis
|