Defective platelet aggregation and increased resistance to thrombosis in purinergic P2Y1 receptor–null mice
| العنوان: | Defective platelet aggregation and increased resistance to thrombosis in purinergic P2Y1 receptor–null mice |
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| المؤلفون: | Anita Eckly, Andrée Dierich, Marianne LeMeur, Monique Freund, Catherine Vial, Catherine Léon, Béatrice Hechler, Philippe Ohlmann, Christian Gachet, Jean-Pierre Cazenave |
| المساهمون: | Biologie et pharmacologie de l'hémostase et de la thrombose, EFS-Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), univOAK, Archive ouverte |
| المصدر: | Journal of Clinical Investigation Journal of Clinical Investigation, 1999, 104 (12), pp.1731-1737. ⟨10.1172/JCI8399⟩ |
| بيانات النشر: | American Society for Clinical Investigation, 1999. |
| سنة النشر: | 1999 |
| مصطلحات موضوعية: | Male, medicine.medical_specialty, P2Y receptor, Bleeding Time, Purinergic P2/*physiology, Biology, P2 receptor, Research Support, Inbred C57BL, Adenylyl cyclase, Mice, chemistry.chemical_compound, P2Y12, Genetic, Internal medicine, Receptors, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Platelet, Platelet activation, Non-U.S. Gov't, Receptor, Adenosine Diphosphate/pharmacology, Thrombosis/*prevention and control, Purinergic receptor, General Medicine, Platelet Activation, Recombination, Endocrinology, chemistry, Female, Platelet Aggregation |
| الوصف: | International audience; ADP is a key agonist in hemostasis and thrombosis. ADP-induced platelet activation involves the purinergic P2Y(1) receptor, which is responsible for shape change through intracellular calcium mobilization. This process also depends on an unidentified P2 receptor (P2cyc) that leads to adenylyl cyclase inhibition and promotes the completion and amplification of the platelet response. P2Y(1)-null mice were generated to define the role of the P2Y(1) receptor and to determine whether the unidentified P2cyc receptor is distinct from P2Y(1). These mice are viable with no apparent abnormalities affecting their development, survival, reproduction, or the morphology of their platelets, and the platelet count in these animals is identical to that of wild-type mice. However, platelets from P2Y(1)-deficient mice are unable to aggregate in response to usual concentrations of ADP and display impaired aggregation to other agonists, while high concentrations of ADP induce platelet aggregation without shape change. In addition, ADP-induced inhibition of adenylyl cyclase still occurs, demonstrating the existence of an ADP receptor distinct from P2Y(1). P2Y(1)-null mice have no spontaneous bleeding tendency but are resistant to thromboembolism induced by intravenous injection of ADP or collagen and adrenaline. Hence, the P2Y(1) receptor plays an essential role in thrombotic states and represents a potential target for antithrombotic drugs. |
| تدمد: | 0021-9738 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::014d0e07837f1255e6f68d0a879550c4Test https://doi.org/10.1172/jci8399Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....014d0e07837f1255e6f68d0a879550c4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00219738 |
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