Premium
Functional Cross‐talk in the Kidney between ß 3 Adrenergic Receptors and NKCC2 in the Thick Ascending Limb of the Loop of Henle
Author(s) -
Carmosino Monica,
Dal Monte Massimo,
Schena Giorgia,
Torretta Silvia,
Gerbino Andrea,
Procino Giuseppe,
Bagnoli Paola,
Svelto Maria
Publication year - 2015
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.29.1_supplement.809.19
Subject(s) - loop of henle , receptor , kidney , adrenergic receptor , loop (graph theory) , anatomy , medicine , biology , endocrinology , microbiology and biotechnology , nephron , mathematics , combinatorics
The thick ascending limb of the loop of Henle (TAL) reabsorbs ∼30% of the filtered NaCl in the kidney, in a process mediated by the apical Na‐K‐2Cl cotransporter NKCC2, which thus plays a crucial role in blood pressure regulation. It is known that catecholamine enhances NaCl reabsorption in the TAL acting through either ß1 or ß2 adrenergic receptors (BAR1 and BAR2). The presence and the possible functional role of ß3 adrenergic receptors (BAR3) in the TAL are still debated. We found that BAR3 are expressed at the basolateral membrane of TAL cells in mouse kidney. Tracking the expression of BAR3 along the nephron, we found that they are expressed also in other vasopressin‐sensitive segments, suggesting their possible role in salt and water homeostasis. Interestingly, we found that NKCC2 phosphorylation, but not NKCC2 protein expression, significantly increased in mouse kidney slices stimulated with the BAR3 selective agonist BRL37344, demonstrating for the first time that the selective activation of BAR3 stimulates NKCC2 activity in the kidney. Of note, mice knock‐out for both BAR1 and BAR2 showed a remarkable increase in NKCC2 phosphorylation compared to the control strain even in resting conditions demonstrating that BAR3, even when expressed without the other subtypes of the beta adrenergic receptors in the TAL, are able to regulate the activity of NKCC2. These data show the physiological relevance of BAR3 in the regulation of NKCC2 activity in the kidney and suggest BAR3 antagonists as possible and novel pharmacological tools for the treatment of hypertension.