K conformation when not activated. They take part in quite a few
K conformation when not activated. They participate in many biological processes, from fighting infectious agentsKeywordsReceptor Aggregation; Platelet Aggregation; Percutaneous Coronary Intervention.Mailing Address: Felipe Josde Andrade Falc Rua Isaac Salazar, 102/902, Tamarineira. HDAC1 review Postal Code D5 Receptor Synonyms 52060-105, Recife, PE – Brazil E-mail: [email protected], [email protected] Manuscript received May perhaps 14, 2012; revised manuscript Could 30, 2012; accepted March 25, 2013.DOI: ten.5935/abc.Falc et al. P2Y12 platelet receptorsReview ArticleFigure 1 – P2 platelet receptors. Reprinted from Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, Alfonso F,Macaya C, Bass TA et al. Variability in individual responsiveness to clopidogrel: clinical implications, management, and future perspectives. J Am CollCardiol. 2007;49(14):1505-16, with permission of Elsevier.The P2X 1 receptors are responsible for a transient conformational transform in platelets, which is connected towards the rapid calcium influx. Therefore, although not capable of sustaining platelet aggregation, they contribute to collagen-induced activation4. P2Y 1 receptors can be discovered in multiple tissues, which includes the heart, blood vessels, smooth muscular cells, nervous tissues, testicles, prostate and ovaries. In response to ADP-mediated activation, calcium is mobilized from platelet storage, major to conformational alter and transient aggregation. This receptor includes a key part within the beginning of ADP-induced activation, but, for the successful stabilization of platelet thrombus, the activation of other receptors is required4,5. P2Y12 receptors, in addition to becoming discovered in platelets, are also present within the microglia, endothelial cells and smooth muscle cells. These receptors possess a central role within the amplification in the aggregation induced by all platelet agonists, for example collagen, thrombin, thromboxane A2, adrenaline and serotonin. Despite that, the agonist together with the highest affinity, as observed with P2Yreceptors, is ADP The intracellular response to its activation . would be the inhibition of cAMP (cyclic adenosine monophosphate) production, vasodilator-stimulated phosphoprotein (VASP) dephosphorylation and GTPase Rap1B and phosphoinositide 3-kinase (PI3-K) activation. The activation of each P2 receptors is important to ADP-induced aggregation, since the selective inhibition of a single receptor results in a crucial reduction in platelet aggregation8. P2Y12 receptor inhibitors Antiplatelet drugs are important in the management of patients submitted to PCI. There are three groups of antiaggregation drugs with established clinical efficacy: cyclooxygenase inhibitors (AAS), P2Y12 receptor inhibitors and glycoprotein IIb/IIIa antagonists9. The P2Y12 receptor is the primary target of oral inhibitory agents, considering that it is directly involved in the amplification of the platelet reactivity required for thrombus formation. There are three classes of P2Y12 receptors: thienopyridines, ATP analogues and ciclopentil-triazolo pyrimidines (Table 1).Arq Bras Cardiol. 2013;101(3):277-Falc et al. P2Y12 platelet receptorsReview ArticleTable 1 – P2Y12 receptor inhibitorsDrug Clopidogrel Prasugrel Cangrelor Ticagrelor Route Oral Oral IV Oral Action Irreversible Hepatic metabolization Irreversible Hepatic metabolization Reversible Direct inhibition Reversible Direct inhibition Dosing (bolus/maintenance) 600 mg 75 mg/d 60 mg ten mg/d 30Kg/min four Kg/min 180 mg 90 mg 12/12 h Peak effect 3h 30 min 1 min 30 min Main studies CURE-PCI CLARITY-P.
