β3 Adrenergic Receptor Agonist Mirabegron Increases AQP2 and NKCC2 Urinary Excretion in OAB Patients: A Pleiotropic Effect of Interest for Patients with X-Linked Nephrogenic Diabetes Insipidus
We previously reported the novel finding that β3-AR is functionally expressed in the renal tubule and shares its cellular localization with the vasopressin receptor AVPR2, whose physiological stimulation triggers antidiuresis by increasing the plasma membrane expression of the water channel AQP2 and...
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/2/1136 |
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| author | Serena Milano Fatima Maqoud Monica Rutigliano Ilenia Saponara Monica Carmosino Andrea Gerbino Giuseppe Lucarelli Michele Battaglia Maria Svelto Giuseppe Procino |
| author_facet | Serena Milano Fatima Maqoud Monica Rutigliano Ilenia Saponara Monica Carmosino Andrea Gerbino Giuseppe Lucarelli Michele Battaglia Maria Svelto Giuseppe Procino |
| author_sort | Serena Milano |
| collection | DOAJ |
| description | We previously reported the novel finding that β3-AR is functionally expressed in the renal tubule and shares its cellular localization with the vasopressin receptor AVPR2, whose physiological stimulation triggers antidiuresis by increasing the plasma membrane expression of the water channel AQP2 and the NKCC2 symporter in renal cells. We also showed that pharmacologic stimulation of β3-AR is capable of triggering antidiuresis and correcting polyuria, in the knockout mice for the AVPR2 receptor, the animal model of human X-linked nephrogenic diabetes insipidus (XNDI), a rare genetic disease still missing a cure. Here, to demonstrate that the same response can be evoked in humans, we evaluated the effect of treatment with the β3-AR agonist mirabegron on AQP2 and NKCC2 trafficking, by evaluating their urinary excretion in a cohort of patients with overactive bladder syndrome, for the treatment of which the drug is already approved. Compared to baseline, treatment with mirabegron significantly increased AQP2 and NKCC2 excretion for the 12 weeks of treatment. This data is a step forward in corroborating the hypothesis that in patients with XNDI, treatment with mirabegron could bypass the inactivation of AVPR2, trigger antidiuresis and correct the dramatic polyuria which is the main hallmark of this disease. |
| first_indexed | 2024-03-09T12:24:33Z |
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| id | doaj.art-28e26f972f904df9847bc9d821223a2d |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T12:24:33Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-28e26f972f904df9847bc9d821223a2d2023-11-30T22:35:56ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01242113610.3390/ijms24021136β3 Adrenergic Receptor Agonist Mirabegron Increases AQP2 and NKCC2 Urinary Excretion in OAB Patients: A Pleiotropic Effect of Interest for Patients with X-Linked Nephrogenic Diabetes InsipidusSerena Milano0Fatima Maqoud1Monica Rutigliano2Ilenia Saponara3Monica Carmosino4Andrea Gerbino5Giuseppe Lucarelli6Michele Battaglia7Maria Svelto8Giuseppe Procino9Department of Biosciences, Biotechnology and Biopharmaceutics, University of Bari, 70125 Bari, ItalyDepartment of Biosciences, Biotechnology and Biopharmaceutics, University of Bari, 70125 Bari, ItalyUrology, Andrology and Kidney Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, ItalyDepartment of Biosciences, Biotechnology and Biopharmaceutics, University of Bari, 70125 Bari, ItalyDepartment of Science, University of Potenza, 85100 Potenza, ItalyDepartment of Biosciences, Biotechnology and Biopharmaceutics, University of Bari, 70125 Bari, ItalyUrology, Andrology and Kidney Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, ItalyUrology, Andrology and Kidney Transplantation Unit, Department of Emergency and Organ Transplantation, University of Bari, 70124 Bari, ItalyDepartment of Biosciences, Biotechnology and Biopharmaceutics, University of Bari, 70125 Bari, ItalyDepartment of Biosciences, Biotechnology and Biopharmaceutics, University of Bari, 70125 Bari, ItalyWe previously reported the novel finding that β3-AR is functionally expressed in the renal tubule and shares its cellular localization with the vasopressin receptor AVPR2, whose physiological stimulation triggers antidiuresis by increasing the plasma membrane expression of the water channel AQP2 and the NKCC2 symporter in renal cells. We also showed that pharmacologic stimulation of β3-AR is capable of triggering antidiuresis and correcting polyuria, in the knockout mice for the AVPR2 receptor, the animal model of human X-linked nephrogenic diabetes insipidus (XNDI), a rare genetic disease still missing a cure. Here, to demonstrate that the same response can be evoked in humans, we evaluated the effect of treatment with the β3-AR agonist mirabegron on AQP2 and NKCC2 trafficking, by evaluating their urinary excretion in a cohort of patients with overactive bladder syndrome, for the treatment of which the drug is already approved. Compared to baseline, treatment with mirabegron significantly increased AQP2 and NKCC2 excretion for the 12 weeks of treatment. This data is a step forward in corroborating the hypothesis that in patients with XNDI, treatment with mirabegron could bypass the inactivation of AVPR2, trigger antidiuresis and correct the dramatic polyuria which is the main hallmark of this disease.https://www.mdpi.com/1422-0067/24/2/1136AQP2NKCC2mirabegronbeta3-adrenoreceptornephrogenic diabetes insipidusdiuresis |
| spellingShingle | Serena Milano Fatima Maqoud Monica Rutigliano Ilenia Saponara Monica Carmosino Andrea Gerbino Giuseppe Lucarelli Michele Battaglia Maria Svelto Giuseppe Procino β3 Adrenergic Receptor Agonist Mirabegron Increases AQP2 and NKCC2 Urinary Excretion in OAB Patients: A Pleiotropic Effect of Interest for Patients with X-Linked Nephrogenic Diabetes Insipidus International Journal of Molecular Sciences AQP2 NKCC2 mirabegron beta3-adrenoreceptor nephrogenic diabetes insipidus diuresis |
| title | β3 Adrenergic Receptor Agonist Mirabegron Increases AQP2 and NKCC2 Urinary Excretion in OAB Patients: A Pleiotropic Effect of Interest for Patients with X-Linked Nephrogenic Diabetes Insipidus |
| title_full | β3 Adrenergic Receptor Agonist Mirabegron Increases AQP2 and NKCC2 Urinary Excretion in OAB Patients: A Pleiotropic Effect of Interest for Patients with X-Linked Nephrogenic Diabetes Insipidus |
| title_fullStr | β3 Adrenergic Receptor Agonist Mirabegron Increases AQP2 and NKCC2 Urinary Excretion in OAB Patients: A Pleiotropic Effect of Interest for Patients with X-Linked Nephrogenic Diabetes Insipidus |
| title_full_unstemmed | β3 Adrenergic Receptor Agonist Mirabegron Increases AQP2 and NKCC2 Urinary Excretion in OAB Patients: A Pleiotropic Effect of Interest for Patients with X-Linked Nephrogenic Diabetes Insipidus |
| title_short | β3 Adrenergic Receptor Agonist Mirabegron Increases AQP2 and NKCC2 Urinary Excretion in OAB Patients: A Pleiotropic Effect of Interest for Patients with X-Linked Nephrogenic Diabetes Insipidus |
| title_sort | β3 adrenergic receptor agonist mirabegron increases aqp2 and nkcc2 urinary excretion in oab patients a pleiotropic effect of interest for patients with x linked nephrogenic diabetes insipidus |
| topic | AQP2 NKCC2 mirabegron beta3-adrenoreceptor nephrogenic diabetes insipidus diuresis |
| url | https://www.mdpi.com/1422-0067/24/2/1136 |
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