ArticleJournal of cellular and molecular medicine2017
The V2 receptor antagonist tolvaptan raises cytosolic calcium and prevents AQP2 trafficking and function: an in vitro and in vivo assessment.
Article in Journal of cellular and molecular medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- Novel Roles of GPCRs in the Renal Collecting Duct.Physiology (Bethesda, Md.) · 2026Review
- Article
- Cross-Species Insights into Autosomal Dominant Polycystic Kidney Disease: Provide an Alternative View on Research Advancement.International journal of molecular sciences · 2024Review
- Novel Potential Therapeutic Targets in Autosomal Dominant Polycystic Kidney Disease from the Perspective of Cell Polarity and Fibrosis.Biomolecules & therapeutics · 2024Review
- Predictive Value of Urinary Aquaporin 2 for Acute Kidney Injury in Patients with Acute Decompensated Heart Failure.Biomedicines · 2022Article
- Nephronophthisis-Pathobiology and Molecular Pathogenesis of a Rare Kidney Genetic Disease.Genes · 2021Review
- Urinary Aquaporin 2 as a Potential Indicator Predicting Tolvaptan Response in Patients With ADPKD.Kidney international reports · 2021Article
- Olive Leaf Extract (OLE) impaired vasopressin-induced aquaporin-2 trafficking through the activation of the calcium-sensing receptor.Scientific reports · 2021Article
- The Bioinformatics Analysis of Aldosterone-Producing Adenoma and Verification of Differentially Expressed Genes.International journal of endocrinology · 2021Article
- A snake toxin as a theranostic agent for the type 2 vasopressin receptor.Theranostics · 2020Article
- Lixivaptan, a New Generation Diuretic, Counteracts Vasopressin-Induced Aquaporin-2 Trafficking and Function in Renal Collecting Duct Cells.International journal of molecular sciences · 2019Article
- Arginine vasopressin modulates electrical activity and calcium homeostasis in pulmonary vein cardiomyocytes.Journal of biomedical science · 2019Article
- Novel molecular mechanisms in the inhibition of adrenal aldosterone synthesis: Action of tolvaptan via vasopressin VBritish journal of pharmacology · 2019Article
- Evidence for Effective Multiple KFrontiers in pharmacology · 2019Article
- Vasopressin-aquaporin-2 pathway: recent advances in understanding water balance disorders.F1000Research · 2019Review
- Activation of Calcium-Sensing Receptor increases intracellular calcium and decreases cAMP and mTOR in PKD1 deficient cells.Scientific reports · 2018Article
- Activation of the Calcium-Sensing Receptor Corrects the Impaired Mitochondrial Energy Status Observed in Renal Polycystin-1 Knockdown Cells Modeling Autosomal Dominant Polycystic Kidney Disease.Frontiers in molecular biosciences · 2018Article
- Astroglial Modulation of Hydromineral Balance and Cerebral Edema.Frontiers in molecular neuroscience · 2018Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tolvaptan, a selective vasopressin V2 receptor antagonist, is a new generation diuretic. Its clinical efficacy is in principle due to impaired vasopressin-regulated water reabsorption via aquaporin-2 (AQP2). Nevertheless, no direct in vitro evidence that tolvaptan prevents AQP2-mediated water transport, nor that this pathway is targeted in vivo in patients with syndrome of inappropriate antidiuresis (SIAD) has been provided. The effects of tolvaptan on the vasopressin-cAMP/PKA signalling cascade were investigated in MDCK cells expressing endogenous V2R and in mouse kidney. In MDCK, tolvaptan prevented dDAVP-induced increase in ser256-AQP2 and osmotic water permeability. A similar effect on ser256-AQP2 was found in V1aR -/- mice, thus confirming the V2R selectively. Of note, calcium calibration in MDCK showed that tolvaptan per se caused calcium mobilization from the endoplasmic reticulum resulting in a significant increase in basal intracellular calcium. This effect was only observed in cells expressing the V2R, indicating that it requires the tolvaptan-V2R interaction. Consistent with this finding, tolvaptan partially reduced the increase in ser256-AQP2 and the water permeability in response to forskolin, a direct activator of adenylyl cyclase (AC), suggesting that the increase in intracellular calcium is associated with an inhibition of the calcium-inhibitable AC type VI. Furthermore, tolvaptan treatment reduced AQP2 excretion in two SIAD patients and normalized plasma sodium concentration. These data represent the first detailed demonstration of the central role of AQP2 blockade in the aquaretic effect of tolvaptan and underscore a novel effect in raising intracellular calcium that can be of significant clinical relevance.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.