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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...

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Autores principales: Procino, Giuseppe, Carmosino, Monica, Milano, Serena, Dal Monte, Massimo, Schena, Giorgia, Mastrodonato, Maria, Gerbino, Andrea, Bagnoli, Paola, Svelto, Maria
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2016
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.
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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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