Olive Leaf Extract (OLE) impaired vasopressin-induced aquaporin-2 trafficking through the activation of the calcium-sensing receptor
Abstract Vasopressin (AVP) increases water permeability in the renal collecting duct through the regulation of aquaporin-2 (AQP2) trafficking. Several disorders, including hypertension and inappropriate antidiuretic hormone secretion (SIADH), are associated with abnormalities in water homeostasis. I...
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| Format: | Article |
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Nature Portfolio
2021-02-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-021-83850-5 |
| _version_ | 1818435837199646720 |
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| author | Marianna Ranieri Annarita Di Mise Mariangela Centrone Mariagrazia D’Agostino Stine Julie Tingskov Maria Venneri Tommaso Pellegrino Graziana Difonzo Francesco Caponio Rikke Norregaard Giovanna Valenti Grazia Tamma |
| author_facet | Marianna Ranieri Annarita Di Mise Mariangela Centrone Mariagrazia D’Agostino Stine Julie Tingskov Maria Venneri Tommaso Pellegrino Graziana Difonzo Francesco Caponio Rikke Norregaard Giovanna Valenti Grazia Tamma |
| author_sort | Marianna Ranieri |
| collection | DOAJ |
| description | Abstract Vasopressin (AVP) increases water permeability in the renal collecting duct through the regulation of aquaporin-2 (AQP2) trafficking. Several disorders, including hypertension and inappropriate antidiuretic hormone secretion (SIADH), are associated with abnormalities in water homeostasis. It has been shown that certain phytocompounds are beneficial to human health. Here, the effects of the Olive Leaf Extract (OLE) have been evaluated using in vitro and in vivo models. Confocal studies showed that OLE prevents the vasopressin induced AQP2 translocation to the plasma membrane in MCD4 cells and rat kidneys. Incubation with OLE decreases the AVP-dependent increase of the osmotic water permeability coefficient (Pf). To elucidate the possible effectors of OLE, intracellular calcium was evaluated. OLE increases the intracellular calcium through the activation of the Calcium Sensing Receptor (CaSR). NPS2143, a selective CaSR inhibitor, abolished the inhibitory effect of OLE on AVP-dependent water permeability. In vivo experiments revealed that treatment with OLE increases the expression of the CaSR mRNA and decreases AQP2 mRNA paralleled by an increase of the AQP2-targeting miRNA-137. Together, these findings suggest that OLE antagonizes vasopressin action through stimulation of the CaSR indicating that this extract may be beneficial to attenuate disorders characterized by abnormal CaSR signaling and affecting renal water reabsorption. |
| first_indexed | 2024-12-14T16:59:13Z |
| format | Article |
| id | doaj.art-12cb165d760144b5a15b242e983724db |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-14T16:59:13Z |
| publishDate | 2021-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-12cb165d760144b5a15b242e983724db2022-12-21T22:53:53ZengNature PortfolioScientific Reports2045-23222021-02-0111111310.1038/s41598-021-83850-5Olive Leaf Extract (OLE) impaired vasopressin-induced aquaporin-2 trafficking through the activation of the calcium-sensing receptorMarianna Ranieri0Annarita Di Mise1Mariangela Centrone2Mariagrazia D’Agostino3Stine Julie Tingskov4Maria Venneri5Tommaso Pellegrino6Graziana Difonzo7Francesco Caponio8Rikke Norregaard9Giovanna Valenti10Grazia Tamma11Department of Bioscience, Biotechnology and Biopharmaceutics, University of Bari Aldo MoroDepartment of Bioscience, Biotechnology and Biopharmaceutics, University of Bari Aldo MoroDepartment of Bioscience, Biotechnology and Biopharmaceutics, University of Bari Aldo MoroDepartment of Bioscience, Biotechnology and Biopharmaceutics, University of Bari Aldo MoroDepartment of Clinical Medicine, Aarhus UniversityDepartment of Bioscience, Biotechnology and Biopharmaceutics, University of Bari Aldo MoroDepartment of Bioscience, Biotechnology and Biopharmaceutics, University of Bari Aldo MoroDepartment of Soil, Plant and Food Sciences, University of Bari Aldo MoroDepartment of Soil, Plant and Food Sciences, University of Bari Aldo MoroDepartment of Clinical Medicine, Aarhus UniversityDepartment of Bioscience, Biotechnology and Biopharmaceutics, University of Bari Aldo MoroDepartment of Bioscience, Biotechnology and Biopharmaceutics, University of Bari Aldo MoroAbstract Vasopressin (AVP) increases water permeability in the renal collecting duct through the regulation of aquaporin-2 (AQP2) trafficking. Several disorders, including hypertension and inappropriate antidiuretic hormone secretion (SIADH), are associated with abnormalities in water homeostasis. It has been shown that certain phytocompounds are beneficial to human health. Here, the effects of the Olive Leaf Extract (OLE) have been evaluated using in vitro and in vivo models. Confocal studies showed that OLE prevents the vasopressin induced AQP2 translocation to the plasma membrane in MCD4 cells and rat kidneys. Incubation with OLE decreases the AVP-dependent increase of the osmotic water permeability coefficient (Pf). To elucidate the possible effectors of OLE, intracellular calcium was evaluated. OLE increases the intracellular calcium through the activation of the Calcium Sensing Receptor (CaSR). NPS2143, a selective CaSR inhibitor, abolished the inhibitory effect of OLE on AVP-dependent water permeability. In vivo experiments revealed that treatment with OLE increases the expression of the CaSR mRNA and decreases AQP2 mRNA paralleled by an increase of the AQP2-targeting miRNA-137. Together, these findings suggest that OLE antagonizes vasopressin action through stimulation of the CaSR indicating that this extract may be beneficial to attenuate disorders characterized by abnormal CaSR signaling and affecting renal water reabsorption.https://doi.org/10.1038/s41598-021-83850-5 |
| spellingShingle | Marianna Ranieri Annarita Di Mise Mariangela Centrone Mariagrazia D’Agostino Stine Julie Tingskov Maria Venneri Tommaso Pellegrino Graziana Difonzo Francesco Caponio Rikke Norregaard Giovanna Valenti Grazia Tamma Olive Leaf Extract (OLE) impaired vasopressin-induced aquaporin-2 trafficking through the activation of the calcium-sensing receptor Scientific Reports |
| title | Olive Leaf Extract (OLE) impaired vasopressin-induced aquaporin-2 trafficking through the activation of the calcium-sensing receptor |
| title_full | Olive Leaf Extract (OLE) impaired vasopressin-induced aquaporin-2 trafficking through the activation of the calcium-sensing receptor |
| title_fullStr | Olive Leaf Extract (OLE) impaired vasopressin-induced aquaporin-2 trafficking through the activation of the calcium-sensing receptor |
| title_full_unstemmed | Olive Leaf Extract (OLE) impaired vasopressin-induced aquaporin-2 trafficking through the activation of the calcium-sensing receptor |
| title_short | Olive Leaf Extract (OLE) impaired vasopressin-induced aquaporin-2 trafficking through the activation of the calcium-sensing receptor |
| title_sort | olive leaf extract ole impaired vasopressin induced aquaporin 2 trafficking through the activation of the calcium sensing receptor |
| url | https://doi.org/10.1038/s41598-021-83850-5 |
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