Document Detail


Trypsin can activate the epithelial sodium channel (ENaC) in microdissected mouse distal nephron.
MedLine Citation:
PMID:  18653483     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Proteases are involved in the processing and activation of the epithelial sodium channel (ENaC). The aim of the present study was to investigate whether the prototypical serine protease trypsin can activate ENaC in microdissected, split-open mouse renal distal tubules. Whole-cell patch-clamp recordings from principal cells of connecting tubules (CNT) or cortical collecting ducts (CCD) demonstrated that addition of trypsin (20 microg/ml) to the bath solution increased the ENaC-mediated amiloride-sensitive whole cell current (DeltaIAmi) in the majority of cells. In contrast, trypsin applied in the presence of an excess of soybean trypsin inhibitor had no stimulatory effect. The DeltaIAmi response to trypsin was variable, ranging from no apparent effect to a twofold increase in DeltaI(Ami) with an average stimulatory effect of 31 or 37% in mice on low-Na+ or standard Na+ diet, respectively. In cultured M-1 mouse collecting duct cells, a robust stimulatory effect of trypsin on DeltaIAmi was only observed in cells pretreated with protease inhibitors. This suggests that endogenous proteases contribute to ENaC activation in renal tubular cells and that the degree of ENaC prestimulation by endogenous proteases determines the magnitude of the stimulatory response to exogenous trypsin. In conclusion, we provide electrophysiological evidence that trypsin can stimulate ENaC activity in native renal mouse tubules. Thus, in the kidney, ENaC stimulation by extracellular proteases may be a relevant regulatory mechanism in vivo.
Authors:
Viatcheslav Nesterov; Anke Dahlmann; Marko Bertog; Christoph Korbmacher
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-07-23
Journal Detail:
Title:  American journal of physiology. Renal physiology     Volume:  295     ISSN:  1931-857X     ISO Abbreviation:  Am. J. Physiol. Renal Physiol.     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-10-10     Completed Date:  2008-12-03     Revised Date:  2011-04-28    
Medline Journal Info:
Nlm Unique ID:  100901990     Medline TA:  Am J Physiol Renal Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  F1052-62     Citation Subset:  IM    
Affiliation:
Institut für Zelluläre und Molekulare Physiologie, Friedrich-Alexander-Universität Erlangen-Nürnberg, Waldstr. 6, 91054 Erlangen, Germany.
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MeSH Terms
Descriptor/Qualifier:
Amiloride / pharmacology
Animals
Aprotinin / pharmacology
Cells, Cultured
Epithelial Sodium Channel / drug effects,  metabolism*
Kidney Tubules, Distal / cytology,  metabolism*
Male
Membrane Potentials / drug effects,  physiology
Mice
Mice, Inbred C57BL
Microdissection
Nephrons / metabolism*
Patch-Clamp Techniques
Serine Endopeptidases / metabolism
Serine Proteinase Inhibitors / pharmacology
Sodium / metabolism
Sodium Channel Blockers / pharmacology
Sodium, Dietary / pharmacology
Trypsin / metabolism*,  pharmacology
Trypsin Inhibitors / pharmacology
Chemical
Reg. No./Substance:
0/Epithelial Sodium Channel; 0/Serine Proteinase Inhibitors; 0/Sodium Channel Blockers; 0/Sodium, Dietary; 0/Trypsin Inhibitors; 2609-46-3/Amiloride; 7440-23-5/Sodium; 9087-70-1/Aprotinin; EC 3.4.21.-/Serine Endopeptidases; EC 3.4.21.4/Trypsin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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