ArticleAmerican journal of physiology. Renal physiology2011
Tolvaptan inhibits ERK-dependent cell proliferation, Cl⁻ secretion, and in vitro cyst growth of human ADPKD cells stimulated by vasopressin.
Article in American journal of physiology. Renal physiology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers.
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Who cites it
105 citing papers in PubMed, 152 citations in OpenAlex.
- Preservation of kidney function irrelevant of total kidney volume growth rate with tolvaptan treatment in patients with autosomal dominant polycystic kidney disease.Clinical and experimental nephrology · 2021Trial
- Long-Term Administration of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease.Clinical journal of the American Society of Nephrology : CJASN · 2018Trial
- Multicenter, open-label, extension trial to evaluate the long-term efficacy and safety of early versus delayed treatment with tolvaptan in autosomal dominant polycystic kidney disease: the TEMPO 4:4 Trial.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2018Trial
- Trial
- Pharmacokinetics and Pharmacodynamics of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease: Phase 2 Trials for Dose Selection in the Pivotal Phase 3 Trial.Journal of clinical pharmacology · 2017Trial
- Urine Osmolality, Response to Tolvaptan, and Outcome in Autosomal Dominant Polycystic Kidney Disease: Results from the TEMPO 3:4 Trial.Journal of the American Society of Nephrology : JASN · 2017Trial
- Effect of Tolvaptan in Autosomal Dominant Polycystic Kidney Disease by CKD Stage: Results from the TEMPO 3:4 Trial.Clinical journal of the American Society of Nephrology : CJASN · 2016Trial
- Safety study of somatostatin analogue octreotide for autosomal dominant polycystic kidney disease in Japan.Clinical and experimental nephrology · 2015Trial
- Tolvaptan in patients with autosomal dominant polycystic kidney disease.The New England journal of medicine · 2012Trial
- Dysregulated ferritin and iron homeostasis in autosomal dominant polycystic kidney disease.American journal of physiology. Renal physiology · 2026Article
- Vaptans: A Narrative Review of Pharmacokinetics, Pharmacogenetics, and Clinical Applications.Cells · 2026Review
- Collecting Duct-Targeted Lipid Nanoparticles DeliverbioRxiv : the preprint server for biology · 2026Article
- Modelling kidney cystogenesis using human kidney tubuloid cultures.BMC molecular and cell biology · 2026Article
- TLR2 Activation Enhances Inflammatory Signaling and Accelerates Cyst Growth and Renal Fibrosis in Polycystic Kidney Disease Mice.International journal of molecular sciences · 2026Article
- Identification of non-oncology drugs with activity against inflammatory and triple-negative breast cancer cell lines.Oncology letters · 2026Article
- Effect of tolvaptan on the prognosis of patients with rapidly progressive autosomal dominant polycystic kidney disease: a prospective open-label study.Frontiers in medicine · 2026Article
- Article
- Long-Term Effects of Tolvaptan Therapy on Total Kidney Volume and Renal Function in Patients with Autosomal Dominant Polycystic Kidney Disease: A Single-Center Experience.Journal of clinical medicine · 2025Article
- Activation of toll-like receptor 2 promotes the expression of inflammatory mediators and cell proliferation of human polycystic kidney disease cells.Cellular signalling · 2025Article
- Safety and efficacy of tolvaptan in real‑world Japanese patients with autosomal dominant polycystic kidney disease: final results of SLOW‑PKD surveillance.Clinical and experimental nephrology · 2025Observational
45 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 4 countries.
Funding
Abstract
In autosomal dominant polycystic kidney disease (ADPKD), arginine vasopressin (AVP) accelerates cyst growth by stimulating cAMP-dependent ERK activity and epithelial cell proliferation and by promoting Cl(-)-dependent fluid secretion. Tolvaptan, a V2 receptor antagonist, inhibits the renal effects of AVP and slows cyst growth in PKD animals. Here, we determined the effect of graded concentrations of tolvaptan on intracellular cAMP, ERK activity, cell proliferation, and transcellular Cl(-) secretion using human ADPKD cyst epithelial cells. Incubation of ADPKD cells with 10(-9) M AVP increased intracellular cAMP and stimulated ERK and cell proliferation. Tolvaptan caused a concentration-dependent inhibition of AVP-induced cAMP production with an apparent IC(50) of ∼10(-10) M. Correspondingly, tolvaptan inhibited AVP-induced ERK signaling and cell proliferation. Basolateral application of AVP to ADPKD cell monolayers grown on permeable supports caused a sustained increase in short-circuit current that was completely blocked by the Cl(-) channel blocker CFTR(inh-172), consistent with AVP-induced transepithelial Cl(-) secretion. Tolvaptan inhibited AVP-induced Cl(-) secretion and decreased in vitro cyst growth of ADPKD cells cultured within a three-dimensional collagen matrix. These data demonstrate that relatively low concentrations of tolvaptan inhibit AVP-stimulated cell proliferation and Cl(-)-dependent fluid secretion by human ADPKD cystic cells.
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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.