ArticleThe Journal of pharmacology and experimental therapeutics2013
Prasugrel metabolites inhibit neutrophil functions.
Article in The Journal of pharmacology and experimental therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Effect of Potent P2YBioMed research international · 2018Pooled it
- Platelet P2YBritish journal of pharmacology · 2024Review
- Secreted folate receptor γ drives fibrogenesis in metabolic dysfunction-associated steatohepatitis by amplifying TGFβ signaling in hepatic stellate cells.Science translational medicine · 2023Article
- Extracellular Acetylated Histone 3.3 Induces Inflammation and Lung Tissue Damage.Biomolecules · 2023Article
- The Signaling Pathway of the ADP Receptor P2YInternational journal of molecular sciences · 2023Review
- Physiologic roles of P2 receptors in leukocytes.Journal of leukocyte biology · 2022Review
- Sex-related differences in the response of anti-platelet drug therapies targeting purinergic signaling pathways in sepsis.Frontiers in immunology · 2022Article
- Ticagrelor Exerts Immune-Modulatory Effect by Attenuating Neutrophil Extracellular Traps.International journal of molecular sciences · 2020Article
- A Review of Antiplatelet Activity of Traditional Medicinal Herbs on Integrative Medicine Studies.Evidence-based complementary and alternative medicine : eCAM · 2019Review
- Role of Protein Kinase C-delta in regulating platelet activation and platelet-leukocyte interaction during sepsis.PloS one · 2018Article
- P2Y12 Receptor Modulates Sepsis-Induced Inflammation.Arteriosclerosis, thrombosis, and vascular biology · 2016Article
- Effects of P2Y12 receptor antagonists beyond platelet inhibition--comparison of ticagrelor with thienopyridines.British journal of pharmacology · 2016Review
- LPS-induced systemic inflammation is more severe in P2Y12 null mice.Journal of leukocyte biology · 2014Article
- The role of P2Y₁₂ receptor and activated platelets during inflammation.Current drug targets · 2014Review
- Erosive arthritis and hepatic granuloma formation induced by peptidoglycan polysaccharide in rats is aggravated by prasugrel treatment.PloS one · 2013Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Clopidogrel and prasugrel belong to a thienopyridine class of oral antiplatelet drugs that, after having been metabolized in the liver, can inhibit platelet function by irreversibly antagonizing the P2Y(12) receptor. Furthermore, thienopyridines influence numerous inflammatory conditions, but their effects on neutrophils have not been evaluated, despite the important role of these cells in inflammation. Therefore, we investigated the effect of prasugrel metabolites on neutrophils to further clarify the role of thienopyridines in inflammation. Interestingly, a prasugrel metabolite mixture, produced in vitro using rat liver microsomes, significantly inhibited N-formyl-methionyl-leucyl-phenylalanine (fMLP)- and platelet-activating factor (PAF)-induced neutrophil activation. More specifically, prasugrel metabolites inhibited neutrophil transmigration, CD16 surface expression, and neutrophil-platelet aggregation. Moreover, prasugrel metabolite pretreatment also significantly decreased fMLP- or PAF-induced extracellular-signal-regulated kinase phosphorylation as well as calcium mobilization. To determine the target of prasugrel in neutrophils, the role of both P2Y(12) and P2Y(13) receptors was studied using specific reversible antagonists, AR-C69931MX and MRS2211, respectively. Neither antagonist had any direct effect on the agonist-induced neutrophil functional responses. Our findings indicate that prasugrel metabolites may directly target neutrophils and inhibit their activation, suggesting a possible explanation for their anti-inflammatory effects previously observed. However, these metabolites do not act through either the P2Y(12) or P2Y(13) receptor in neutrophils.
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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.