ArticleEuropean journal of pharmacology2010
Hydroxyurea stimulates the release of ATP from rabbit erythrocytes through an increase in calcium and nitric oxide production.
Article in European journal of pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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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
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- A systematic review of known mechanisms of hydroxyurea-induced fetal hemoglobin for treatment of sickle cell disease.Expert review of hematology · 2015Pooled it
- Endothelial Nitric Oxide Synthase-Dependent Mechanism of Hydroxyurea-Induced S-Phase Arrest in Erythroid Cells.Antioxidants (Basel, Switzerland) · 2026Article
- Hope on the Horizon: New and Future Therapies for Sickle Cell Disease.Journal of clinical medicine · 2023Review
- Red blood cells in type 1 diabetes and multiple sclerosis and technologies to measure their emerging roles.Journal of translational autoimmunity · 2022Review
- Biochemical Evaluation of the Effects of Hydroxyurea in Vitro on Red Blood Cells.Antioxidants (Basel, Switzerland) · 2021Article
- From Experiments to Simulation: Shear-Induced Responses of Red Blood Cells to Different Oxygen Saturation Levels.Frontiers in physiology · 2019Article
- Hydroxyurea attenuates oxidative, metabolic, and excitotoxic stress in rat hippocampal neurons and improves spatial memory in a mouse model of Alzheimer's disease.Neurobiology of aging · 2018Article
- Purinergic control of red blood cell metabolism: novel strategies to improve red cell storage quality.Blood transfusion = Trasfusione del sangue · 2017Review
- Mathematical model for shear stress dependent NO and adenine nucleotide production from endothelial cells.Nitric oxide : biology and chemistry · 2016Article
- Blood cells: an historical account of the roles of purinergic signalling.Purinergic signalling · 2015Review
- Regulation of extracellular ATP in human erythrocytes infected with Plasmodium falciparum.PloS one · 2014Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Hydroxyurea, a proven therapy for sickle cell disease, is known to improve blood flow and reduce vaso-occlusive crises, although its exact mechanism of action is not clear. The objective of this study was to determine if hydroxyurea results in an increase of ATP release from the red blood cell (RBC) via the drug's ability to stimulate nitric oxide (NO) production in these cells. A system enabling the flow of RBCs through microbore tubing was used to investigate ATP release from the RBC. Incubation of rabbit RBCs (7% hct) with 50 microM hydroxyurea resulted in a significant increase in the release of ATP from these cells. This level of ATP release was not detected in the absence of flow. Studies also showed that increments in hydroxyurea and NO (from spermine NONOate) resulted in an initial increase in ATP release, followed by a decrease in this release at higher concentrations of hydroxyurea and the NO donor. Incubation with L-NAME abolished the effect of the hydroxyurea, suggesting that NO production by the RBC was involved. Indeed, in the presence of 50 microM hydroxyurea, the amount of total Ca(2+) measured (by atomic absorption spectroscopy) in a 7% solution of RBCs increased from 363+/-47 ng/ml and 530+/-52 ng/ml. Finally, EPR studies suggest that an increase in nitrosylated Hb in the RBC is only measured for those studies involving hydroxyurea and a Ca(2+)-containing buffer.
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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.