1,211
Views
64
CrossRef citations to date
0
Altmetric
Spotlight Article

P2Y12 receptor in platelet activation

& , PhD
Pages 54-58 | Received 15 Apr 2010, Accepted 26 May 2010, Published online: 13 Jan 2011

References

  • Jin J, Kunapuli SP. Coactivation of two different G protein-coupled receptors is essential for ADP-induced platelet aggregation. Proc Natl Acad Sci U S A 1998; 95: 8070–8074
  • Jin J, Daniel JL, Kunapuli SP. Molecular basis for ADP-induced platelet activation. II. The P2Y1 receptor mediates ADP-induced intracellular calcium mobilization and shape change in platelets. J Biol Chem 1998; 273: 2030–2034
  • Fabre JE, Nguyen M, Latour A, Keifer JA, Audoly LP, Coffman TM, et al. Decreased platelet aggregation, increased bleeding time and resistance to thromboembolism in P2Y1-deficient mice. Nat Med 1999; 5: 1199–1202
  • Hollopeter G, Jantzen HM, Vincent D, Li G, England L, Ramakrishnan V, et al. Identification of the platelet ADP receptor targeted by antithrombotic drugs. Nature 2001; 409: 202–207
  • Zhang FL, Luo L, Gustafson E, Lachowicz J, Smith M, Qiao X, et al. ADP is the cognate ligand for the orphan G protein-coupled receptor SP1999. J Biol Chem 2001; 276: 8608–8615
  • Dorsam RT, Kunapuli SP. Central role of the P2Y12 receptor in platelet activation. J Clin Invest 2004; 113: 340–345
  • Kahner BN, Shankar H, Murugappan S, Prasad GL, Kunapuli SP. Nucleotide receptor signaling in platelets. J Thromb Haemost 2006; 4: 2317–2326
  • Savi P, Herbert JM. Clopidogrel and ticlopidine: P2Y12 adenosine diphosphate-receptor antagonists for the prevention of atherothrombosis. Semin Thromb Hemost 2005; 31: 174–183
  • Cattaneo M, Zighetti ML, Lombardi R, Martinez C, Lecchi A, Conley PB, et al. Molecular bases of defective signal transduction in the platelet P2Y12 receptor of a patient with congenital bleeding. Proc Natl Acad Sci U S A 2003; 100: 1978–1983
  • Foster CJ, Prosser DM, Agans JM, Zhai Y, Smith MD, Lachowicz JE, et al. Molecular identification and characterization of the platelet ADP receptor targeted by thienopyridine antithrombotic drugs. J Clin Invest 2001; 107: 1591–1598
  • Jantzen HM, Milstone DS, Gousset L, Conley PB, Mortensen RM. Impaired activation of murine platelets lacking G alpha(i2). J Clin Invest 2001; 108: 477–483
  • Remijn JA, Wu YP, Jeninga EH, MJ IJ, van Willigen G, de Groot PG, et al. Role of ADP receptor P2Y(12) in platelet adhesion and thrombus formation in flowing blood. Arterioscler Thromb Vasc Biol 2002; 22: 686–691
  • Andre P, Delaney SM, LaRocca T, Vincent D, DeGuzman F, Jurek M, et al. P2Y12 regulates platelet adhesion/activation, thrombus growth, and thrombus stability in injured arteries. J Clin Invest 2003; 112: 398–406
  • Daniel JL, Dangelmaier C, Jin J, Kim YB, Kunapuli SP. Role of intracellular signaling events in ADP-induced platelet aggregation. Thromb Haemost 1999; 82: 1322–1326
  • Kim S, Jin J, Kunapuli SP. Akt activation in platelets depends on Gi signaling pathways. J Biol Chem 2004; 279: 4186–4195
  • Kamae T, Shiraga M, Kashiwagi H, Kato H, Tadokoro S, Kurata Y, et al. Critical role of ADP interaction with P2Y12 receptor in the maintenance of alpha(IIb)beta3 activation: association with Rap1B activation. J Thromb Haemost 2006; 4: 1379–1387
  • Stefanini L, Roden RC, Bergmeier W. CalDAG-GEFI is at the nexus of calcium-dependent platelet activation. Blood 2009; 114: 2506–2514
  • Kauffenstein G, Bergmeier W, Eckly A, Ohlmann P, Leon C, Cazenave JP, et al. The P2Y(12) receptor induces platelet aggregation through weak activation of the alpha(IIb)beta(3) integrin–a phosphoinositide 3-kinase-dependent mechanism. FEBS Lett 2001; 505: 281–290
  • Dangelmaier C, Jin J, Smith JB, Kunapuli SP. Potentiation of thromboxane A2-induced platelet secretion by Gi signaling through the phosphoinositide-3 kinase pathway. Thromb Haemost 2001; 85: 341–348
  • Hirsch E, Bosco O, Tropel P, Laffargue M, Calvez R, Altruda F, et al. Resistance to thromboembolism in PI3Kgamma-deficient mice. Faseb J 2001; 15: 2019–2021
  • Maier U, Babich A, Nurnberg B. Roles of non-catalytic subunits in gbetagamma-induced activation of class I phosphoinositide 3-kinase isoforms beta and gamma. J Biol Chem 1999; 274: 29311–29317
  • Schoenwaelder SM, Ono A, Sturgeon S, Chan SM, Mangin P, Maxwell MJ, et al. Identification of a unique co-operative phosphoinositide 3-kinase signaling mechanism regulating integrin alpha IIb beta 3 adhesive function in platelets. J Biol Chem 2007; 282: 28648–28658
  • Canobbio I, Stefanini L, Cipolla L, Ciraolo E, Gruppi C, Balduini C, et al. Genetic evidence for a predominant role of PI3Kbeta catalytic activity in ITAM- and integrin-mediated signaling in platelets. Blood 2009; 114: 2193–2196
  • Becker RC, Gurbel PA. Platelet P2Y12 receptor antagonist pharmacokinetics and pharmacodynamics: A foundation for distinguishing mechanisms of bleeding and anticipated risk for platelet-directed therapies. Thromb Haemost 2010; 103: 535–544
  • Niitsu Y, Jakubowski JA, Sugidachi A, Asai F. Pharmacology of CS-747 (prasugrel, LY640315), a novel, potent antiplatelet agent with in vivo P2Y12 receptor antagonist activity. Semin Thromb Hemost 2005; 31: 184–194
  • Wiviott SD, Braunwald E, McCabe CH, Montalescot G, Ruzyllo W, Gottlieb S, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357: 2001–2015
  • Springthorpe B, Bailey A, Barton P, Birkinshaw TN, Bonnert RV, Brown RC, et al. From ATP to AZD6140: the discovery of an orally active reversible P2Y12 receptor antagonist for the prevention of thrombosis. Bioorg Med Chem Lett 2007; 17: 6013–6018
  • Storey RF, Husted S, Harrington RA, Heptinstall S, Wilcox RG, Peters G, et al. Inhibition of platelet aggregation by AZD6140, a reversible oral P2Y12 receptor antagonist, compared with clopidogrel in patients with acute coronary syndromes. J Am Coll Cardiol 2007; 50: 1852–1856
  • Wallentin L, Becker RC, Budaj A, Cannon CP, Emanuelsson H, Held C, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361: 1045–1057
  • Michelson AD. New P2Y12 antagonists. Curr Opin Hematol 2009; 16: 371–377
  • Wang YX, Vincelette J, da Cunha V, Martin-McNulty B, Mallari C, Fitch RM, et al. A novel P2Y(12) adenosine diphosphate receptor antagonist that inhibits platelet aggregation and thrombus formation in rat and dog models. Thromb Haemost 2007; 97: 847–855
  • Bryant J, Post JM, Alexander S, Wang YX, Kent L, Schirm S, et al. Novel P2Y12 adenosine diphosphate receptor antagonists for inhibition of platelet aggregation (I): in vitro effects on platelets. Thromb Res 2008; 122: 523–532

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.