Trial reportThe Journal of biological chemistry2012
Heat shock protein 90 inhibitors reduce trafficking of ATP-gated P2X1 receptors and human platelet responsiveness.
Trial report in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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
12 citing papers in PubMed, 28 citations in OpenAlex.
- Pharmacologic dissection of the overlapping impact of heat shock protein family members on platelet function.Journal of thrombosis and haemostasis : JTH · 2020Article
- Effects of purine-scaffold inhibitors on HUVECs: Involvement of the purinergic pathway and interference with ATP. Implications for preventing the adverse effects of extracellular Grp94.Biochemistry and biophysics reports · 2019Article
- Organization of ATP-gated P2X1 receptor intracellular termini in apo and desensitized states.The Journal of general physiology · 2019Article
- P2XThe Journal of physiology · 2018Article
- Endotoxin-induced autocrine ATP signaling inhibits neutrophil chemotaxis through enhancing myosin light chain phosphorylation.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- ATP from synaptic terminals and astrocytes regulates NMDA receptors and synaptic plasticity through PSD-95 multi-protein complex.Scientific reports · 2016Article
- HSP90 Regulation of P2X7 Receptor Function Requires an Intact Cytoplasmic C-Terminus.Molecular pharmacology · 2016Article
- Heat shock protein 70 regulates platelet integrin activation, granule secretion and aggregation.American journal of physiology. Cell physiology · 2016Article
- Blood cells: an historical account of the roles of purinergic signalling.Purinergic signalling · 2015Review
- Purinergic control of inflammation and thrombosis: Role of P2X1 receptors.Computational and structural biotechnology journal · 2015Review
- Amplification of human platelet activation by surface pannexin-1 channels.Journal of thrombosis and haemostasis : JTH · 2014Article
- The trafficking and targeting of P2X receptors.Frontiers in cellular neuroscience · 2013Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
We have used selective inhibitors to determine whether the molecular chaperone heat shock protein 90 (HSP90) has an effect on both recombinant and native human P2X1 receptors. P2X1 receptor currents in HEK293 cells were reduced by ∼70-85% by the selective HSP90 inhibitor geldanamycin (2 μM, 20 min). This was associated with a speeding in the time course of desensitization as well as a reduction in cell surface expression. Imaging in real time of photoactivatable GFP-tagged P2X receptors showed that they are highly mobile. Geldanamycin almost abolished this movement for P2X1 receptors but had no effect on P2X2 receptor trafficking. P2X1/2 receptor chimeras showed that the intracellular N and C termini were involved in geldanamycin sensitivity. Geldanamycin also inhibited native P2X1 receptor-mediated responses. Platelet P2X1 receptors play an important role in hemostasis, contribute to amplification of signaling to a range of stimuli including collagen, and are novel targets for antithrombotic therapies. Platelet P2X1 receptor-, but not P2Y1 receptor-, mediated increases in intracellular calcium were reduced by 40-45% following HSP90 inhibition with geldanamycin or radicicol. Collagen stimulation leads to ATP release from platelets, and calcium increases to low doses of collagen were also reduced by ∼40% by the HSP90 inhibitors consistent with an effect on P2X1 receptors. These studies suggest that HSP90 inhibitors may be as effective as selective antagonists in regulating platelet P2X1 receptors, and their potential effects on hemostasis should be considered in clinical studies.
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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.