ArticleJournal of the American Society of Nephrology : JASN2013
Small-molecule screening identifies modulators of aquaporin-2 trafficking.
Article in Journal of the American Society of Nephrology : JASN, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- Regulation of renal aquaporins: implications in tubular epithelial integrity.Biochemical Society transactions · 2026Review
- Goreisan promotes diuresis by regulating the abundance of aquaporin 2 phosphorylated at serine 269 through calcium-sensing receptor activation.Scientific reports · 2024Article
- Intracellular sites of AQP2 S256 phosphorylation identified using inhibitors of the AQP2 recycling itinerary.American journal of physiology. Renal physiology · 2023Article
- Signaling Mechanisms and Pharmacological Modulators Governing Diverse Aquaporin Functions in Human Health and Disease.International journal of molecular sciences · 2022Review
- Aurora Kinase A Is Involved in Controlling the Localization of Aquaporin-2 in Renal Principal Cells.International journal of molecular sciences · 2022Article
- Systems Biology of the Vasopressin V2 Receptor: New Tools for Discovery of Molecular Actions of a GPCR.Annual review of pharmacology and toxicology · 2022Review
- Updates and Perspectives on Aquaporin-2 and Water Balance Disorders.International journal of molecular sciences · 2021Review
- Aquaporin 2 regulation: implications for water balance and polycystic kidney diseases.Nature reviews. Nephrology · 2021Review
- Article
- Small molecules for modulating the localisation of the water channel aquaporin-2-disease relevance and perspectives for targeting local cAMP signalling.Naunyn-Schmiedeberg's archives of pharmacology · 2019Review
- An Antifungal for Antidiuresis?Journal of the American Society of Nephrology : JASN · 2019Article
- Fluconazole Increases Osmotic Water Transport in Renal Collecting Duct through Effects on Aquaporin-2 Trafficking.Journal of the American Society of Nephrology : JASN · 2019Article
- Article
- Bimodal antagonism of PKA signalling by ARHGAP36.Nature communications · 2016Article
- The Trafficking of the Water Channel Aquaporin-2 in Renal Principal Cells-a Potential Target for Pharmacological Intervention in Cardiovascular Diseases.Frontiers in pharmacology · 2016Review
- High-throughput chemical screening identifies AG-490 as a stimulator of aquaporin 2 membrane expression and urine concentration.American journal of physiology. Cell physiology · 2014Article
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Authors and funding
15 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In the principal cells of the renal collecting duct, arginine vasopressin (AVP) stimulates the synthesis of cAMP, leading to signaling events that culminate in the phosphorylation of aquaporin-2 water channels and their redistribution from intracellular domains to the plasma membrane via vesicular trafficking. The molecular mechanisms that control aquaporin-2 trafficking and the consequent water reabsorption, however, are not completely understood. Here, we used a cell-based assay and automated immunofluorescence microscopy to screen 17,700 small molecules for inhibitors of the cAMP-dependent redistribution of aquaporin-2. This approach identified 17 inhibitors, including 4-acetyldiphyllin, a selective blocker of vacuolar H(+)-ATPase that increases the pH of intracellular vesicles and causes accumulation of aquaporin-2 in the Golgi compartment. Although 4-acetyldiphyllin did not inhibit forskolin-induced increases in cAMP formation and downstream activation of protein kinase A (PKA), it did prevent cAMP/PKA-dependent phosphorylation at serine 256 of aquaporin-2, which triggers the redistribution to the plasma membrane. It did not, however, prevent cAMP-induced changes to the phosphorylation status at serines 261 or 269. Last, we identified the fungicide fluconazole as an inhibitor of cAMP-mediated redistribution of aquaporin-2, but its target in this pathway remains unknown. In conclusion, our screening approach provides a method to begin dissecting molecular mechanisms underlying AVP-mediated water reabsorption, evidenced by our identification of 4-acetyldiphyllin as a modulator of aquaporin-2 trafficking.
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