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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Signaling pathways involved in the rapid biphasic effect of aldosterone on Na+/H(+)exchanger in rat proximal tubule cells

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Leite-Dellova, Deise C. A. [1] ; Szriber, Shirley J. [1] ; Merighe, Giovana K. F. [2] ; Polidoro, Juliano Z. [3] ; Reboucas, Nancy A. [3] ; Oliveira-Souza, Maria [3] ; de Mello-Aires, Margarida [3]
Total Authors: 7
[1] Univ Sao Paulo, Fac Anim Sci & Food Engn, Dept Vet Med, 225 Duque Caxias Norte Ave, BR-13635900 Pirassununga - Brazil
[2] Univ Sao Paulo, Fac Anim Sci & Food Engn, Basic Sci, Pirassununga - Brazil
[3] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo - Brazil
Total Affiliations: 3
Document type: Journal article
Web of Science Citations: 2

The receptors and signaling pathways for nongenomic effects of aldosterone (Aldo) on the proximal Na+/H+ exchanger are still unknown; therefore, the aim of this study was to investigate the mineralocorticoid receptor (MR) and/or glucocorticoid receptor (GR) participation in rapid Aldo effects on NHE1 (basolateral Na+H+ exchanger isoform) and cytosolic calcium concentration ({[}Ca2+](i)). In addition, phospholipase C (PLC), protein kinase C (PKC), and mitogen-activated protein kinase kinase (MEK) involvement in signaling pathways of such effects was evaluated, using immortalized proximal tubule cells of rat (IRPTC) as an experimental model. MR and GR expression was investigated using reverse transcription polymerase chain reaction and immunoblotting. The intracellular pH recovery rate (after acid loading) and {[}Ca-2+](i) were determined by the probes BCECF-AM and FORA 2-AM, respectively. Aldo (10(-12)M) promoted a moderate increase in {[}Ca2+](i) and stimulation of NHE1, whereas Aldo (10(-6)M) greatly increased the {[}Ca2+](i), but inhibited the NHE1. BAPTA-AM (a calcium chelator), GR antagonism and inhibition of PLC, PKC and MEK pathway abolished the biphasic and dose-dependent effect of Aldo on NHE1 and decreased the {[}Ca2+](i); whereas MR do not appear to participate in this rapid signaling in IRPTC cells. The reduction of GR content, by gene silencing, abolished the Aldo effect on NHE1, in low concentration, confirming the importance of this receptor in the rapid modulation of proximal sodium and hydrogen transports. (AU)

FAPESP's process: 13/23087-4 - Molecular and functional study of membrane transporters
Grantee:Gerhard Malnic
Support type: Research Projects - Thematic Grants
FAPESP's process: 17/02020-0 - Mechanisms involved in the transition from post-ischemic acute kidney injury to chronic kidney disease: contribution of angiotensin II and albumin
Grantee:Maria Oliveira de Souza
Support type: Regular Research Grants
FAPESP's process: 11/19967-3 - Study of aldosterone nongenomic effects: receptor and signaling pathways in the proximal tubule and participation in the kidney injury mechanism
Grantee:Deise Carla Almeida Leite Dellova
Support type: Regular Research Grants
FAPESP's process: 13/19569-3 - Effects of endothelin-3 and leptin in renal morphology and function in vivo: involvement of the intrarenal renin-angiotensin system
Grantee:Maria Oliveira de Souza
Support type: Regular Research Grants