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β3 adrenergic receptor in the kidney may be a new player in sympathetic regulation of renal function.
- Source :
-
Kidney international [Kidney Int] 2016 Sep; Vol. 90 (3), pp. 555-67. Date of Electronic Publication: 2016 May 17. - Publication Year :
- 2016
-
Abstract
- To date, the study of the sympathetic regulation of renal function has been restricted to the important contribution of β1- and β2-adrenergic receptors (ARs). Here we investigate the expression and the possible physiologic role of β3-adrenergic receptor (β3-AR) in mouse kidney. The β3-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 β3-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 β3-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 β3-AR stimulation in the kidney. Hence, β3-AR agonism might be useful to bypass AVPR2-inactivating mutations.<br /> (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Adrenergic beta-3 Receptor Agonists pharmacology
Adrenergic beta-3 Receptor Antagonists pharmacology
Aminophenols pharmacology
Animals
Aquaporin 2 metabolism
Cyclic AMP metabolism
Electrolytes urine
Ethanolamines pharmacology
Fluorescent Antibody Technique
Glomerular Filtration Rate physiology
Isoquinolines pharmacology
Kidney Tubules metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Receptors, Adrenergic, beta-3 genetics
Receptors, Vasopressin genetics
Receptors, Vasopressin metabolism
Solute Carrier Family 12, Member 1 metabolism
Sulfonamides pharmacology
Kidney Tubules physiology
Receptors, Adrenergic, beta-3 physiology
Renal Elimination physiology
Sympathetic Nervous System physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1523-1755
- Volume :
- 90
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Kidney international
- Publication Type :
- Academic Journal
- Accession number :
- 27206969
- Full Text :
- https://doi.org/10.1016/j.kint.2016.03.020