دورية أكاديمية
أعرض في EDS

The β3-AR agonist BRL37344 ameliorates the main symptoms of X-linked nephrogenic diabetes insipidus in the mouse model of the disease.

التفاصيل البيبلوغرافية
العنوان: The β3-AR agonist BRL37344 ameliorates the main symptoms of X-linked nephrogenic diabetes insipidus in the mouse model of the disease.
المؤلفون: Milano S; Department of Biosciences, Biotechnologies and Environment, University of Bari, Bari, Italy.; Department of Sciences, University of Basilicata, Potenza, Italy., Saponara I; Department of Biosciences, Biotechnologies and Environment, University of Bari, Bari, Italy., Gerbino A; Department of Biosciences, Biotechnologies and Environment, University of Bari, Bari, Italy., Carmosino M; Department of Sciences, University of Basilicata, Potenza, Italy., Svelto M; Department of Biosciences, Biotechnologies and Environment, University of Bari, Bari, Italy., Procino G; Department of Biosciences, Biotechnologies and Environment, University of Bari, Bari, Italy.
المصدر: Journal of cellular and molecular medicine [J Cell Mol Med] 2024 Apr; Vol. 28 (8), pp. e18301.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101083777 Publication Model: Print Cited Medium: Internet ISSN: 1582-4934 (Electronic) Linking ISSN: 15821838 NLM ISO Abbreviation: J Cell Mol Med Subsets: MEDLINE
أسماء مطبوعة: Publication: Oxford, England : Wiley-Blackwell
Original Publication: Bucharest : "Carol Davila" University Press, 2000-
مواضيع طبية MeSH: Adrenergic beta-3 Receptor Agonists*/pharmacology , Adrenergic beta-3 Receptor Agonists*/therapeutic use, Male ; Animals ; Mice, Inbred C57BL ; Disease Models, Animal ; Antidiuretic Agents/pharmacology ; Antidiuretic Agents/therapeutic use ; Kidney Concentrating Ability/drug effects ; Polydipsia/drug therapy ; Polydipsia/etiology
مستخلص: X-linked nephrogenic diabetes insipidus (X-NDI) is a rare congenital disease caused by inactivating mutations of the vasopressin type-2 receptor (AVPR2), characterized by impaired renal concentrating ability, dramatic polyuria, polydipsia and risk of dehydration. The disease, which still lacks a cure, could benefit from the pharmacologic stimulation of other GPCRs, activating the cAMP-intracellular pathway in the kidney cells expressing the AVPR2. On the basis of our previous studies, we here hypothesized that the β3-adrenergic receptor could be such an ideal candidate. We evaluated the effect of continuous 24 h stimulation of the β3-AR 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-NDI. Here we demonstrate that the β3-AR agonism exhibits a potent antidiuretic effect. The strong improvement in symptoms of X-NDI produced by a single i.p. injection of BRL37344 (1 mg/kg) was limited to 3 h but repeated administrations in the 24 h, mimicking the effect of a slow-release preparation, promoted a sustained antidiuretic effect, reducing the 24 h 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-NDI mice. Taken together, these data suggest that human β3-AR agonists might represent an effective possible treatment strategy for X-NDI.
(© 2024 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)
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معلومات مُعتمدة: POC01_00072 Ministero dell'Università e della Ricerca; GGP15083 Fondazione Telethon
فهرسة مساهمة: Keywords: (3–6) vasopressin; BRL37344; antidiuresis; beta‐3 adrenoreceptor; kidney; nephrogenic diabetes insipidus
المشرفين على المادة: 0 (Adrenergic beta-3 Receptor Agonists)
0 (Antidiuretic Agents)
تواريخ الأحداث: Date Created: 20240423 Date Completed: 20240423 Latest Revision: 20240513
رمز التحديث: 20240513
مُعرف محوري في PubMed: PMC11037407
DOI: 10.1111/jcmm.18301
PMID: 38652212
قاعدة البيانات: MEDLINE
الوصف
تدمد:1582-4934
DOI:10.1111/jcmm.18301