Activation of the Thiazide-Sensitive Sodium-Chloride Cotransporter by Beta3-Adrenoreceptor in the Distal Convoluted Tubule.

beta3-adrenoreceptor distal convoluted tubule sodium-chloride cotransporter sympathetic regulation thiazide-sensitive Na-Cl cotransporter

Journal

Frontiers in physiology
ISSN: 1664-042X
Titre abrégé: Front Physiol
Pays: Switzerland
ID NLM: 101549006

Informations de publication

Date de publication:
2021
Historique:
received: 15 04 2021
accepted: 16 07 2021
entrez: 6 9 2021
pubmed: 7 9 2021
medline: 7 9 2021
Statut: epublish

Résumé

We previously showed that the beta-3 adrenergic receptor (BAR3) is expressed in most segments of the nephron where its agonism promotes a potent antidiuretic effect. We localized BAR3 in distal convoluted tubule (DCT) cells expressing the thiazide-sensitive sodium-chloride cotransporter (NCC). Aim of this study is to investigate the possible functional role of BAR3 on NCC modulation in DCT cells. Here, we found that, in mice, the knockout of BAR3 was paralleled by a significant attenuation of NCC phosphorylation, paralleled by reduced expression and activation of STE-20/SPS1-related proline-alanine-rich kinase (SPAK) and WNKs the main kinases involved in NCC activation. Conversely, in BAR1/2 knockout mice, we found reduced NCC abundance with no changes in the phosphorylation state of NCC. Moreover, selective BAR3 agonism promotes both SPAK and NCC activation in wild-type mouse kidney slices. In conclusion, our findings suggest a novel role for BAR3 in the regulation of NCC in DCT.

Identifiants

pubmed: 34483955
doi: 10.3389/fphys.2021.695824
pmc: PMC8414899
doi:

Types de publication

Journal Article

Langues

eng

Pagination

695824

Informations de copyright

Copyright © 2021 Milano, Carmosino, Gerbino, Saponara, Lapi, Dal Monte, Bagnoli, Svelto and Procino.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Serena Milano (S)

Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy.

Monica Carmosino (M)

Department of Sciences, University of Basilicata, Potenza, Italy.

Andrea Gerbino (A)

Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy.

Ilenia Saponara (I)

Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy.

Dominga Lapi (D)

Department of Biology, University of Pisa, Pisa, Italy.

Massimo Dal Monte (M)

Department of Biology, University of Pisa, Pisa, Italy.

Paola Bagnoli (P)

Department of Biology, University of Pisa, Pisa, Italy.

Maria Svelto (M)

Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy.

Giuseppe Procino (G)

Department of Biosciences, Biotechnologies and Biopharmaceutics, University of Bari, Bari, Italy.

Classifications MeSH