ArticlePloS one2014
Inhibition of platelet activation and thrombus formation by adenosine and inosine: studies on their relative contribution and molecular modeling.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 74 citations in OpenAlex.
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- Adenosine and adenosine receptors: a "double-edged sword" in cardiovascular system.Frontiers in pharmacology · 2025Review
- Novel Agonists of Adenosine Receptors in Animal Model of Acute Myocardial Infarction.Drug design, development and therapy · 2024Article
- 8-Aminopurines in the Cardiovascular and Renal Systems and Beyond.Hypertension (Dallas, Tex. : 1979) · 2023Review
- Effects of Platelet Agonists and Priming on the Formation of Platelet Populations.Thrombosis and haemostasis · 2022Article
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- Integrated microbiome and metabolome analysis reveals the potential therapeutic mechanism ofFrontiers in cellular and infection microbiology · 2022Article
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- Antiplatelet Activity of Tetramethylpyrazine via Regulation of the P2Y12 Receptor Downstream Signaling Pathway.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- Synthesis and evaluation of adenosine derivatives as AEuropean journal of medicinal chemistry · 2021Article
- Metabolomic Profile in Venous Thromboembolism (VTE).Metabolites · 2021Review
- Adenosine Receptor Agonist HE-NECA Enhances Antithrombotic Activities of Cangrelor and Prasugrel in vivo by Decreasing of Fibrinogen Density in Thrombus.International journal of molecular sciences · 2021Article
- Case Report: Can Inhaled Adenosine Attenuate COVID-19?Frontiers in pharmacology · 2021Article
- Antiplatelet activity and chemical analysis of leaf and fruit extracts from Aristotelia chilensis.PloS one · 2021Article
- Platelet Anti-Aggregant Activity and Bioactive Compounds of Ultrasound-Assisted Extracts from Whole and Seedless Tomato Pomace.Foods (Basel, Switzerland) · 2020Article
- Therapeutic Perspectives of Adenosine Deaminase Inhibition in Cardiovascular Diseases.Molecules (Basel, Switzerland) · 2020Review
- Mitoquinone (MitoQ) Inhibits Platelet Activation Steps by Reducing ROS Levels.International journal of molecular sciences · 2020Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe inhibitory effect of adenosine on platelet aggregation is abrogated after the addition of adenosine-deaminase. Inosine is a naturally occurring nucleoside degraded from adenosine.
objectivesThe mechanisms of antiplatelet action of adenosine and inosine in vitro and in vivo, and their differential biological effects by molecular modeling were investigated.
resultsAdenosine (0.5, 1 and 2 mmol/L) inhibited phosphatidylserine exposure from 52±4% in the control group to 44±4 (p<0.05), 29±2 (p<0.01) and 20±3% (p<0.001). P-selectin expression in the presence of adenosine 0.5, 1 and 2 mmol/L was inhibited from 32±4 to 27±2 (p<0.05), 14±3 (p<0.01) and 9±3% (p<0.001), respectively. At the concentrations tested, only inosine to 4 mmol/L had effect on platelet P-selectin expression (p<0.05). Adenosine and inosine inhibited platelet aggregation and ATP release stimulated by ADP and collagen. Adenosine and inosine reduced collagen-induced platelet adhesion and aggregate formation under flow. At the same concentrations adenosine inhibited platelet aggregation, decreased the levels of sCD40L and increased intraplatelet cAMP. In addition, SQ22536 (an adenylate cyclase inhibitor) and ZM241385 (a potent adenosine receptor A2A antagonist) attenuated the effect of adenosine on platelet aggregation induced by ADP and intraplatelet level of cAMP. Adenosine and inosine significantly inhibited thrombosis formation in vivo (62±2% occlusion at 60 min [n = 6, p<0.01] and 72±1.9% occlusion at 60 min, [n = 6, p<0.05], respectively) compared with the control (98±2% occlusion at 60 min, n = 6). A2A is the adenosine receptor present in platelets; it is known that inosine is not an A2A ligand. Docking of adenosine and inosine inside A2A showed that the main difference is the formation by adenosine of an additional hydrogen bond between the NH2 of the adenine group and the residues Asn253 in H6 and Glu169 in EL2 of the A2A receptor.
conclusionTherefore, adenosine and inosine may represent novel agents lowering the risk of arterial thrombosis.
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