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β 3 ‐adrenoreceptor as a new player in sympathetic regulation of the acid‐base homeostasis in the kidney.
Author(s) -
Milano Serena,
Gerbino Andrea,
Carmosino Monica,
Svelto Maria,
Procino Giuseppe
Publication year - 2020
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.2020.34.s1.05271
Subject(s) - nephron , medicine , endocrinology , chemistry , homeostasis , kidney , stimulation , sodium–hydrogen antiporter , reabsorption , secretion , pendrin , agonist , receptor , biology , biochemistry , sodium , organic chemistry , transporter , gene
Sympathetic nervous system has an important role in the regulation of renal function. We previously showed that, in mouse, the β 3 ‐adrenoreceptor (β 3 ‐AR) localizes in most of the nephron segments and its selective agonism promotes a potent antidiuretic effect. Here, we report the expression of β 3 ‐AR in distal nephron intercalated cells (ICs). Co‐localization study of β 3 ‐AR either with H + ‐ATPase or Cl − /HCO 3 − exchanger pendrin in mouse kidney showed that the β 3 ‐AR was expressed in H + ‐secreting type A, in HCO 3 − secreting type B, and in non‐A non B ICs. To unveil a possible role of β 3 ‐AR in systemic pH regulation, we analyzed the urine pH of wild type (wt) and β 3 ‐AR knock‐out (ko) mice. We found that the urine pH of β 3 ‐AR ko mice was significantly higher than wt mice. In line with these results, localization and expression analysis showed that the renal H + ‐ATPase significantly decreased in β 3 ‐AR ko mice compared to wt mice supporting the idea that H + secretion is partially blunted in these animals. Next, we investigated in kidney cells (M1‐β 3 ‐AR) the effects of β 3 ‐AR stimulation on the activity of H + ‐ATPase monitoring the intracellular pH with the pH‐sensitive dye BCECF. Of note, exposure of M1‐β 3 ‐AR cells to a selective β 3 ‐AR agonist induced a 2.5 fold increase of H + ‐ATPase activity compared with resting cells and this effect was prevented by a selective β 3 ‐AR antagonist or by the H + ‐ATPase inhibitor bafilomycin. Moreover, β 3 ‐AR agonism promoted H + ‐ATPase apical expression in M1‐β 3 ‐AR cells. In addition, the PKA inhibitor H89 abolished the stimulatory effect of β 3 ‐AR agonism, demonstrating the involvement of the cAMP/PKA pathway. We conclude that the modulation of H + ‐ATPase activity in renal ICs by endogenous β 3 ‐AR agonists may play an addition physiological role in hormonal control of systemic acid‐base homeostasis. Support or Funding Information Telethon (project # GGP15083)