ArticleProceedings of the National Academy of Sciences of the United States of America2006
The active metabolite of Clopidogrel disrupts P2Y12 receptor oligomers and partitions them out of lipid rafts.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers, 5 of them syntheses 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
109 citing papers in PubMed, 5 syntheses or guidelines pooled it, 311 citations in OpenAlex.
- Effects of Cilostazol-Based Triple Antiplatelet Therapy Versus Dual Antiplatelet Therapy After Coronary Drug-Eluting Stent Implantation: An Updated Meta-Analysis of the Randomized Controlled Trials.Clinical drug investigation · 2019Pooled it
- The clinical outcomes of triple antiplatelet therapy versus dual antiplatelet therapy for high-risk patients after coronary stent implantation: a meta-analysis of 11 clinical trials and 9,553 patients.Drug design, development and therapy · 2016Pooled it
- Comparing the effectiveness and safety between triple antiplatelet therapy and dual antiplatelet therapy in type 2 diabetes mellitus patients after coronary stents implantation: a systematic review and meta-analysis of randomized controlled trials.BMC cardiovascular disorders · 2015Pooled it
- The effectiveness and safety of triple-antiplatelet treatment based on cilostazol for patients receiving percutaneous coronary intervention: a meta-analysis.Clinical cardiology · 2012Pooled it
- Cytochrome P450 2C19*2 polymorphism and cardiovascular recurrences in patients taking clopidogrel: a meta-analysis.The pharmacogenomics journal · 2011Pooled it
- Prasugrel but not high dose clopidogrel overcomes the lansoprazole neutralizing effect of P2Y12 inhibition: Results of the randomized DOSAPI study.European journal of clinical pharmacology · 2014Trial
- Extending MMPBSA for membrane proteins: Addressing P2YBiophysical journal · 2026Article
- ReDisulphID: A discovery platform for thiol redox sensors identifies a druggable site regulating p53 activation.Redox biology · 2026Article
- Effect of triple versus dual antiplatelet therapy in patients undergoing percutaneous intervention: systematic review and meta-analysis with GRADE system.Annals of medicine and surgery (2012) · 2026Article
- Clopidogrel Influences Fracture Healing Under Ischemic Conditions.Biomedicines · 2025Article
- How selective antagonists and genetic modification have helped characterise the expression and functions of vascular P2Y receptors.Purinergic signalling · 2025Review
- Review
- Oral P2YEuropean cardiology · 2025Review
- One immune cell to bind them all: platelet contribution to neurodegenerative disease.Molecular neurodegeneration · 2024Review
- Pharmacological characterization of P2Y receptor subtypes - an update.Purinergic signalling · 2024Review
- Platelet P2YBritish journal of pharmacology · 2024Review
- METTL7A (TMT1A) and METTL7B (TMT1B) Are Responsible for AlkylDrug metabolism and disposition: the biological fate of chemicals · 2023Article
- The Signaling Pathway of the ADP Receptor P2YInternational journal of molecular sciences · 2023Review
- Platelet P2YBMC biology · 2023Article
- Altered purinergic receptor expression in the frontal cortex in schizophrenia.Schizophrenia (Heidelberg, Germany) · 2022Article
49 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
11 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
P2Y12, a G protein-coupled receptor that plays a central role in platelet activation has been recently identified as the receptor targeted by the antithrombotic drug, clopidogrel. In this study, we further deciphered the mechanism of action of clopidogrel and of its active metabolite (Act-Met) on P2Y12 receptors. Using biochemical approaches, we demonstrated the existence of homooligomeric complexes of P2Y12 receptors at the surface of mammalian cells and in freshly isolated platelets. In vitro treatment with Act-Met or in vivo oral administration to rats with clopidogrel induced the breakdown of these oligomers into dimeric and monomeric entities in P2Y12 expressing HEK293 and platelets respectively. In addition, we showed the predominant association of P2Y12 oligomers to cell membrane lipid rafts and the partitioning of P2Y12 out of rafts in response to clopidogrel and Act-Met. The raft-associated P2Y12 oligomers represented the functional form of the receptor, as demonstrated by binding and signal transduction studies. Finally, using a series of receptors individually mutated at each cysteine residue and a chimeric P2Y12/P2Y13 receptor, we pointed out the involvement of cysteine 97 within the first extracellular loop of P2Y12 in the mechanism of action of Act-Met.
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