ArticleMolecular pharmacology2009
Inhibition of aquaporin-1 and aquaporin-4 water permeability by a derivative of the loop diuretic bumetanide acting at an internal pore-occluding binding site.
Article in Molecular pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
86 citing papers in PubMed, 1 synthesis or guideline pooled it, 162 citations in OpenAlex.
- Efficacy of bumetanide in animal models of ischemic stroke: a systematic review and meta-analysis.Aging · 2024Pooled it
- Aquaporin membrane channels in the hepatobiliary tract: a model of complexity and clinical implications in health and disease.Internal and emergency medicine · 2026Review
- Aquaporin dysfunction and impaired brain interstitial fluid clearance in Alzheimer's disease - an integrative review.Frontiers in cellular neuroscience · 2026Review
- Diuretic inhibition of experimental myopia implicates retinal ion-driven efflux in the regulation of ocular growth.Frontiers in medicine · 2026Article
- Aquaporins: a novel perspective in the treatment of lung diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Aquaporin-4 in Stroke and Brain Edema-Friend or Foe?International journal of molecular sciences · 2025Review
- Aquaporins in Acute Brain Injury: Insights from Clinical and Experimental Studies.Biomedicines · 2025Review
- Distinctive roles of aquaporins and novel therapeutic opportunities against cancer.RSC medicinal chemistry · 2025Review
- The Expanding Role of Aquaporin-1, Aquaporin-3 and Aquaporin-5 as Transceptors: Involvement in Cancer Development and Potential Druggability.International journal of molecular sciences · 2025Review
- Article
- Update on the intriguing roles of AQP4 expression and redistribution in the progression and treatment of glioma.Annals of medicine · 2024Review
- Metabolic Dysfunction in Idiopathic Intracranial Hypertension: Current Theories and Updates.Aging and disease · 2024Review
- Aquaporin-1 and Osmosis: From Physiology to Precision in Peritoneal Dialysis.Journal of the American Society of Nephrology : JASN · 2024Review
- Article
- Functional aspects of the brain lymphatic drainage system in aging and neurodegenerative diseases.Journal of biomedical research · 2024Article
- Toward New AQP4 Inhibitors: ORI-TRN-002.International journal of molecular sciences · 2024Article
- Article
- Aquaporins and Ion Channels as Dual Targets in the Design of Novel Glioblastoma Therapeutics to Limit Invasiveness.Cancers · 2023Review
- Aquaporin-mediated dysregulation of cell migration in disease states.Cellular and molecular life sciences : CMLS · 2023Review
- Aquaporins in Nervous System.Advances in experimental medicine and biology · 2023Article
26 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Aquaporin (AQP) water channels, essential for fluid homeostasis, are expressed in perivascular brain end-feet regions of astroglia (AQP4) and in choroid plexus (AQP1). At a high concentration, the loop diuretic bumetanide has been shown to reduce rat brain edema after ischemic stroke by blocking Na(+)-K(+)-2Cl(-) cotransport. We hypothesized that an additional inhibition of AQP contributes to the protection. We show that osmotic water flux in AQP4-expressing Xenopus laevis oocytes is reduced by extracellular bumetanide (> or =100 microM). The efficacy of block by bumetanide is increased by injection intracellularly. Forty-five synthesized bumetanide derivatives were tested on oocytes expressing human AQP1 and rat AQP4. Of these, one of the most effective was the 4-aminopyridine carboxamide analog, AqB013, which inhibits AQP1 and AQP4 (IC(50) approximately 20 microM, applied extracellularly). The efficacy of block was enhanced by mutagenesis of intracellular AQP4 valine-189 to alanine (V189A, IC(50) approximately 8 microM), confirming the aquaporin as the molecular target of block. In silico docking of AqB013 supported an intracellular candidate binding site in rat AQP4 and suggested that the block involves occlusion of the AQP water pore at the cytoplasmic side. AqB013 at 2 microM had no effect, and 20 microM caused 20% block of human Na(+)-K(+)-2Cl(-) cotransporter activity, in contrast to >90% block of the transporter by bumetanide. AqB013 did not affect X. laevis oocyte Cl(-) currents and did not alter rhythmic electrical conduction in an ex vivo gastric muscle preparation. The identification of AQP-selective pharmacological agents opens opportunities for breakthrough strategies in the treatment of edema and other fluid imbalance disorders.
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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.