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Stimulation of beta adrenergic receptor type‐3 (β 3 ‐AR) in the kidney triggers antidiuresis: physiological implications and possible therapeutic target to treat NDI
Author(s) -
Procino Giuseppe,
Carmosino Monica,
Milano Serena,
Dal Monte Massimo,
Schena Giorgia,
Mastrodonato Maria,
Torretta Silvia,
Gerbino Andrea,
Bagnoli Paola,
Svelto Maria
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.999.1
Subject(s) - endocrinology , medicine , vasopressin , reabsorption , nephron , kidney , aquaporin 2 , stimulation , antidiuretic , diuresis , chemistry , receptor , agonist , vasopressin receptor , urine osmolality , biology , antagonist , mechanical engineering , water channel , engineering , inlet
Background Beta‐adrenergic receptors β 1 ‐AR and β 2 ‐AR regulate important renal functions. However, the presence, localization and possible physiological role of β 3 ‐AR in the kidney is still debated. Methods Immunolocalization of β 3 ‐AR was performed in mouse kidney. Live mouse kidney slices were treated with the β 3 ‐AR selective agonist BRL37344, in the presence or in the absence of the PKA inhibitor H89 or β 3 ‐AR antagonists. To unmask the possible antidiuretic effect of β 3 ‐AR stimulation, we tested the urine concentrating ability of β 3 ‐AR KO mice and injected BRL37344 in wt and vasopressin V2 receptor (V2R) KO mice. Results β 3 ‐AR is expressed at the basolateral membrane of most of the vasopressin‐sensitive nephron segments: thick ascending limb (TAL), distal convolute tubule (DCT) and the cortical/outer medullary collecting duct (CD). Interestingly, in live kidney slices, BRL37344 elicited a vasopressin‐like effect on cAMP production, AQP2 apical expression and KNCC2 phosphorylation/activity. These effects were prevented by β 3 ‐AR antagonists or H89. β 3 ‐AR KO mice showed reduced AQP2 plasma membrane expression, increased diuresis, reduced urine osmolality and increased urine excretion of Na, K and Cl compared to control mice. Moreover, in both wt and V2R‐KO mice, BRL37344 increased Na, K, Cl and water reabsorption and promoted a significant antidiuretic effect. Conclusions Taken together, these findings are of great physiological importance as they uncover an antidiuretic effect of β 3 ‐AR stimulation in the kidney and suggest that β 3 ‐AR agonists might be useful to bypass V2R inactivating mutations. Support or Funding Information Telethon foundation grants n. GGP15083 and n. GGP12040