ENaC inhibition stimulates HCl secretion in the mouse cortical collecting duct. II. Bafilomycin-sensitive H+ secretion.
Am J Physiol Renal Physiol
; 309(3): F259-68, 2015 Aug 01.
Article
em En
| MEDLINE
| ID: mdl-26017972
ABSTRACT
Epithelial Na(+) channel (ENaC) blockade stimulates stilbene-sensitive conductive Cl(-) secretion in the mouse cortical collecting duct (CCD). This study's purpose was to determine the co-ion that accompanies benzamil- and DIDS-sensitive Cl(-) flux. Thus transepithelial voltage, VT, as well as total CO2 (tCO2) and Cl(-) flux were measured in CCDs from aldosterone-treated mice consuming a NaCl-replete diet. We reasoned that if stilbene inhibitors (DIDS) reduce conductive anion secretion they should reduce the lumen-negative VT. However, during ENaC blockade (benzamil, 3 µM), DIDS (100 µM) application to the perfusate reduced net H(+) secretion, which increased the lumen-negative VT. Conversely, ENaC blockade alone stimulated H(+) secretion, which reduced the lumen-negative VT. Application of an ENaC inhibitor to the perfusate reduced the lumen-negative VT, increased intercalated cell intracellular pH, and reduced net tCO2 secretion. However, benzamil did not change tCO2 flux during apical H(+)-ATPase blockade (bafilomycin, 5 nM). The increment in H(+) secretion observed with benzamil application contributes to the fall in VT observed with application of this diuretic. As such, ENaC blockade reduces the lumen-negative VT by inhibiting conductive Na(+) absorption and by stimulating H(+) secretion by type A intercalated cells. In conclusion, 1) in CCDs from aldosterone-treated mice, benzamil application stimulates HCl secretion mediated by the apical H(+)-ATPase and a yet to be identified conductive Cl(-) transport pathway; 2) benzamil-induced HCl secretion is reversed with the application of stilbene inhibitors or H(+)-ATPase inhibitors to the perfusate; and 3) benzamil reduces VT not only by inhibiting conductive Na(+) absorption, but also by stimulating H(+) secretion.
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01-internacional
Base de dados:
MEDLINE
Assunto principal:
Macrolídeos
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Bloqueadores dos Canais de Sódio
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Ácido Clorídrico
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Túbulos Renais Coletores
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article