Busca avançada
Ano de início
Entree
(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Proximal tubule NHE3 activity is inhibited by beta-arrestin-biased angiotensin II type 1 receptor signaling

Texto completo
Autor(es):
Carneiro de Morais, Carla P. [1] ; Polidoro, Juliano Z. [2] ; Ralph, Donna L. [3] ; Pessoa, Thaissa D. [2] ; Oliveira-Souza, Maria [2] ; Barauna, Valerio G. [4] ; Reboucas, Nancy A. [2] ; Malnic, Gerhard [2] ; McDonough, Alicia A. [3] ; Girardi, Adriana C. C. [1]
Número total de Autores: 10
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Sch Med, Heart Inst InCor, BR-05403900 Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Dept Phys & Biophys, BR-05403900 Sao Paulo, SP - Brazil
[3] Univ So Calif, Keck Sch Med, Dept Cell & Neurobiol, Los Angeles, CA 90033 - USA
[4] Univ Fed Espirito Santo, Dept Physiol Sci, Vitoria, Espirito Santo - Brazil
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY; v. 309, n. 8, p. C541-C550, OCT 15 2015.
Citações Web of Science: 5
Resumo

Physiological concentrations of angiotensin II (ANG II) upregulate the activity of Na+/H+ exchanger isoform 3 (NHE3) in the renal proximal tubule through activation of the ANG II type I (AT1) receptor/G protein-coupled signaling. This effect is key for maintenance of extracellular fluid volume homeostasis and blood pressure. Recent findings have shown that selective activation of the beta-arrestin-biased AT1 receptor signaling pathway induces diuresis and natriuresis independent of G protein-mediated signaling. This study tested the hypothesis that activation of this AT1 receptor/beta-arrestin signaling inhibits NHE3 activity in proximal tubule. To this end, we determined the effects of the compound TRV120023, which binds to the AT1R, blocks G-protein coupling, and stimulates beta-arrestin signaling on NHE3 function in vivo and in vitro. NHE3 activity was measured in both native proximal tubules, by stationary microperfusion, and in opossum proximal tubule (OKP) cells, by Na+-dependent intracellular pH recovery. We found that 10(-7) M TRV120023 remarkably inhibited proximal tubule NHE3 activity both in vivo and in vitro. Additionally, stimulation of NHE3 by ANG II was completely suppressed by TRV120023 both in vivo as well as in vitro. Inhibition of NHE3 activity by TRV120023 was associated with a decrease in NHE3 surface expression in OKP cells and with a redistribution from the body to the base of the microvilli in the rat proximal tubule. These findings indicate that biased signaling of the beta-arrestin pathway through the AT1 receptor inhibits NHE3 activity in the proximal tubule at least in part due to changes in NHE3 subcellular localization. (AU)

Processo FAPESP: 13/10619-8 - Dipeptidil peptidase IV como um potencial alvo para a terapia da insuficiência cardíaca
Beneficiário:Adriana Castello Costa Girardi
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 13/50384-0 - Collaborative effort to determine the molecular bases of the blood pressure lowering effects of the incretin hormone GLP-1
Beneficiário:Adriana Castello Costa Girardi
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 12/10146-0 - Mecanismos moleculares da regulação da função tubular proximal na hipertensão arterial
Beneficiário:Adriana Castello Costa Girardi
Linha de fomento: Auxílio à Pesquisa - Regular