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β(3) adrenergic receptor in the kidney may be a new player in sympathetic regulation of renal function
To date, the study of the sympathetic regulation of renal function has been restricted to the important contribution of β(1)- and β(2)-adrenergic receptors (ARs). Here we investigate the expression and the possible physiologic role of β(3)-adrenergic receptor (β(3)-AR) in mouse kidney. The β(3)-AR i...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4996630/ https://www.ncbi.nlm.nih.gov/pubmed/27206969 http://dx.doi.org/10.1016/j.kint.2016.03.020 |
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author | Procino, Giuseppe Carmosino, Monica Milano, Serena Dal Monte, Massimo Schena, Giorgia Mastrodonato, Maria Gerbino, Andrea Bagnoli, Paola Svelto, Maria |
author_facet | Procino, Giuseppe Carmosino, Monica Milano, Serena Dal Monte, Massimo Schena, Giorgia Mastrodonato, Maria Gerbino, Andrea Bagnoli, Paola Svelto, Maria |
author_sort | Procino, Giuseppe |
collection | PubMed |
description | To date, the study of the sympathetic regulation of renal function has been restricted to the important contribution of β(1)- and β(2)-adrenergic receptors (ARs). Here we investigate the expression and the possible physiologic role of β(3)-adrenergic receptor (β(3)-AR) in mouse kidney. The β(3)-AR is expressed in most of the nephron segments that also express the type 2 vasopressin receptor (AVPR2), including the thick ascending limb and the cortical and outer medullary collecting duct. Ex vivo experiments in mouse kidney tubules showed that β(3)-AR stimulation with the selective agonist BRL37344 increased intracellular cAMP levels and promoted 2 key processes in the urine concentrating mechanism. These are accumulation of the water channel aquaporin 2 at the apical plasma membrane in the collecting duct and activation of the Na-K-2Cl symporter in the thick ascending limb. Both effects were prevented by the β(3)-AR antagonist L748,337 or by the protein kinase A inhibitor H89. Interestingly, genetic inactivation of β3-AR in mice was associated with significantly increased urine excretion of water, sodium, potassium, and chloride. Stimulation of β3-AR significantly reduced urine excretion of water and the same electrolytes. Moreover, BRL37344 promoted a potent antidiuretic effect in AVPR2-null mice. Thus, our findings are of potential physiologic importance as they uncover the antidiuretic effect of β(3)-AR stimulation in the kidney. Hence, β(3)-AR agonism might be useful to bypass AVPR2-inactivating mutations. |
format | Online Article Text |
id | pubmed-4996630 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-49966302016-09-01 β(3) adrenergic receptor in the kidney may be a new player in sympathetic regulation of renal function Procino, Giuseppe Carmosino, Monica Milano, Serena Dal Monte, Massimo Schena, Giorgia Mastrodonato, Maria Gerbino, Andrea Bagnoli, Paola Svelto, Maria Kidney Int Basic Research To date, the study of the sympathetic regulation of renal function has been restricted to the important contribution of β(1)- and β(2)-adrenergic receptors (ARs). Here we investigate the expression and the possible physiologic role of β(3)-adrenergic receptor (β(3)-AR) in mouse kidney. The β(3)-AR is expressed in most of the nephron segments that also express the type 2 vasopressin receptor (AVPR2), including the thick ascending limb and the cortical and outer medullary collecting duct. Ex vivo experiments in mouse kidney tubules showed that β(3)-AR stimulation with the selective agonist BRL37344 increased intracellular cAMP levels and promoted 2 key processes in the urine concentrating mechanism. These are accumulation of the water channel aquaporin 2 at the apical plasma membrane in the collecting duct and activation of the Na-K-2Cl symporter in the thick ascending limb. Both effects were prevented by the β(3)-AR antagonist L748,337 or by the protein kinase A inhibitor H89. Interestingly, genetic inactivation of β3-AR in mice was associated with significantly increased urine excretion of water, sodium, potassium, and chloride. Stimulation of β3-AR significantly reduced urine excretion of water and the same electrolytes. Moreover, BRL37344 promoted a potent antidiuretic effect in AVPR2-null mice. Thus, our findings are of potential physiologic importance as they uncover the antidiuretic effect of β(3)-AR stimulation in the kidney. Hence, β(3)-AR agonism might be useful to bypass AVPR2-inactivating mutations. Elsevier 2016-09 /pmc/articles/PMC4996630/ /pubmed/27206969 http://dx.doi.org/10.1016/j.kint.2016.03.020 Text en © 2016 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Basic Research Procino, Giuseppe Carmosino, Monica Milano, Serena Dal Monte, Massimo Schena, Giorgia Mastrodonato, Maria Gerbino, Andrea Bagnoli, Paola Svelto, Maria β(3) adrenergic receptor in the kidney may be a new player in sympathetic regulation of renal function |
title | β(3) adrenergic receptor in the kidney may be a new player in sympathetic regulation of renal function |
title_full | β(3) adrenergic receptor in the kidney may be a new player in sympathetic regulation of renal function |
title_fullStr | β(3) adrenergic receptor in the kidney may be a new player in sympathetic regulation of renal function |
title_full_unstemmed | β(3) adrenergic receptor in the kidney may be a new player in sympathetic regulation of renal function |
title_short | β(3) adrenergic receptor in the kidney may be a new player in sympathetic regulation of renal function |
title_sort | β(3) adrenergic receptor in the kidney may be a new player in sympathetic regulation of renal function |
topic | Basic Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4996630/ https://www.ncbi.nlm.nih.gov/pubmed/27206969 http://dx.doi.org/10.1016/j.kint.2016.03.020 |
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