z-logo
Premium
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

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here