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The disease, which still lacks a cure, could benefit from the pharmacologic stimulation of other GPCRs, activating the cAMP\u2010intracellular pathway in the kidney cells expressing the AVPR2. On the basis of our previous studies, we here hypothesized that the \u03b23\u2010adrenergic receptor could be such an ideal candidate. We evaluated the effect of continuous 24\u2009h stimulation of the \u03b23\u2010AR with the agonist BRL37344 and assessed the effects on urine output, urine osmolarity, water intake and the abundance and activation of the key renal water and electrolyte transporters, in the mouse model of X\u2010NDI. Here we demonstrate that the \u03b23\u2010AR agonism exhibits a potent antidiuretic effect. The strong improvement in symptoms of X\u2010NDI produced by a single i.p. injection of BRL37344 (1\u2009mg\/kg) was limited to 3\u2009h but repeated administrations in the 24\u2009h, mimicking the effect of a slow\u2010release preparation, promoted a sustained antidiuretic effect, reducing the 24\u2009h urine output by 27%, increasing urine osmolarity by 25% and reducing the water intake by 20%. At the molecular level, we show that BRL37344 acted by increasing the phosphorylation of NKCC2, NCC and AQP2 in the renal cell membrane, thereby increasing electrolytes and water reabsorption in the kidney tubule of X\u2010NDI mice. Taken together, these data suggest that human \u03b23\u2010AR agonists might represent an effective possible treatment strategy for X\u2010NDI.<\/jats:p>","DOI":"10.1111\/jcmm.18301","type":"journal-article","created":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T14:51:23Z","timestamp":1713883883000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The <scp>\u03b23\u2010AR<\/scp> agonist <scp>BRL37344<\/scp> ameliorates the main symptoms of X\u2010linked nephrogenic diabetes insipidus in the mouse model of the disease"],"prefix":"10.1111","volume":"28","author":[{"given":"Serena","family":"Milano","sequence":"first","affiliation":[{"name":"Department of Biosciences, Biotechnologies and Environment University of Bari  Bari Italy"},{"name":"Department of Sciences University of Basilicata  Potenza 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