ArticleThe Journal of clinical investigation2000
Nitric oxide and atrial natriuretic factor stimulate cGMP-dependent membrane insertion of aquaporin 2 in renal epithelial cells.
Article in The Journal of clinical investigation, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
84 citing papers in PubMed, 223 citations in OpenAlex.
- Trial
- Effect of tolvaptan on renal water and sodium excretion and blood pressure during nitric oxide inhibition: a dose-response study in healthy subjects.BMC nephrology · 2017Trial
- Effects of atorvastatin on systemic and renal NO dependency in patients with non-diabetic stage II-III chronic kidney disease.British journal of clinical pharmacology · 2014Trial
- Effect of vasopressin antagonism on renal handling of sodium and water and central and brachial blood pressure during inhibition of the nitric oxide system in healthy subjects.BMC nephrology · 2014Trial
- Evaluation of Epithelial Integrity in Human Precision-Cut Kidney Slices.APMIS : acta pathologica, microbiologica, et immunologica Scandinavica · 2026Article
- Regulation of renal aquaporins: implications in tubular epithelial integrity.Biochemical Society transactions · 2026Review
- AQP5 trafficking is regulated by its C-terminal tail and interaction with prolactin-inducible protein.Biology direct · 2025Article
- Ribosomal s6 kinase is a mediator of aquaporin-2 S256 phosphorylation and membrane accumulation after EGFR inhibition with erlotinib.American journal of physiology. Renal physiology · 2025Article
- International expert consensus statement on the diagnosis and management of congenital nephrogenic diabetes insipidus (arginine vasopressin resistance).Nature reviews. Nephrology · 2025Review
- Intracellular sites of AQP2 S256 phosphorylation identified using inhibitors of the AQP2 recycling itinerary.American journal of physiology. Renal physiology · 2023Article
- Genome-Engineered mpkCCDc14 Cells as a New Resource for Studying AQP2.International journal of molecular sciences · 2023Article
- Protein Structure and Modification of Aquaporins.Advances in experimental medicine and biology · 2023Article
- Loss of Pten in Renal Tubular Cells Leads to Water Retention by Upregulating AQP2.Kidney diseases (Basel, Switzerland) · 2023Article
- LRBA is essential for urinary concentration and body water homeostasis.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Simultaneous stabilization of actin cytoskeleton in multiple nephron-specific cells protects the kidney from diverse injury.Nature communications · 2022Article
- Updates and Perspectives on Aquaporin-2 and Water Balance Disorders.International journal of molecular sciences · 2021Review
- Actin-related protein 2/3 complex plays a critical role in the aquaporin-2 exocytotic pathway.American journal of physiology. Renal physiology · 2021Article
- A Novel Fluorogenic Assay for the Detection of Nephrotoxin-Induced Oxidative Stress in Live Cells and Renal Tissue.ACS sensors · 2021Article
- Pdcd10-Stk24/25 complex controls kidney water reabsorption by regulating Aqp2 membrane targeting.JCI insight · 2021Article
- Treatment of Nephrogenic Diabetes Insipidus Patients With cGMP-Stimulating Drugs Does Not Mitigate Polyuria or Increase Urinary Concentrating Ability.Kidney international reports · 2020Article
24 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
In collecting duct principal cells, aquaporin 2 (AQP2) is shuttled from intracellular vesicles to the plasma membrane upon vasopressin (VP) stimulation. VP activates adenylyl cyclase, increases intracellular cAMP, activating protein kinase A (PKA) to phosphorylate AQP2 on the COOH-terminal residue, serine 256. Using rat kidney slices and LLC-PK1 cells stably expressing AQP2 (LLC-AQP2 cells), we now show that AQP2 trafficking can be stimulated by cAMP-independent pathways. In these systems, the nitric oxide (NO) donors sodium nitroprusside (SNP) and NONOate and the NO synthase substrate L-arginine mimicked the effect of VP, stimulating relocation of AQP2 from cytoplasmic vesicles to the plasma membrane. Unlike VP, these other agents did not increase intracellular cAMP. However, SNP increased intracellular cGMP, and exogenous cGMP stimulated AQP2-membrane insertion. Atrial natriuretic factor, which signals via cGMP, also stimulated AQP2 translocation. The VP and SNP effects were blocked by the kinase inhibitor H89. SNP did not stimulate membrane insertion of AQP2 in LLC-PK1 cells expressing the phosphorylation-deficient mutant 256SerAla-AQP2, indicating that phosphorylation of Ser256 is required for signaling. Both PKA and cGMP-dependent protein kinase G phosphorylated AQP2 on this COOH-terminal residue in vitro. These results demonstrate a novel, cAMP-independent and cGMP-dependent pathway for AQP2 membrane insertion in renal epithelial 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.