G-Protein-Coupled receptors signaling pathways in new antiplatelet drug development

Paul A. Gurbel, Athan Kuliopulos, Udaya S. Tantry

Research output: Contribution to journalArticlepeer-review

49 Scopus citations


Platelet G-protein-coupled receptors influence platelet function by mediating the response to various agonists, including ADP, thromboxane A2 , and thrombin. Blockade of the ADP receptor, P2Y12 , in combination with cyclooxygenase-1 inhibition by aspirin has been among the most widely used pharmacological strategies to reduce cardiovascular event occurrence in high-risk patients. The latter dual pathway blockade strategy is one of the greatest advances in the field of cardiovascular medicine. In addition to P2Y12 , the platelet thrombin receptor, protease activated receptor-1, has also been recently targeted for inhibition. Blockade of protease activated receptor-1 has been associated with reduced thrombotic event occurrence when added to a strategy using P2Y12 and cyclooxygenase-1 inhibition. At this time, the relative contributions of these G-protein-coupled receptor signaling pathways to in vivo thrombosis remain incompletely defined. The observation of treatment failure in ?10% of high-risk patients treated with aspirin and potent P2Y12 inhibitors provides the rationale for targeting novel pathways mediating platelet function. Targeting intracellular signaling downstream from G-protein-coupled receptor receptors with phosphotidylionisitol 3-kinase and Gq inhibitors are among the novel strategies under investigation to prevent arterial ischemic event occurrence. Greater understanding of the mechanisms of G-protein-coupled receptor-mediated signaling may allow the tailoring of antiplatelet therapy.

Original languageEnglish (US)
Pages (from-to)500-512
Number of pages13
JournalArteriosclerosis, thrombosis, and vascular biology
Issue number3
StatePublished - Mar 2015


  • GTP-binding proteins
  • blood platelet
  • coronary disease
  • purinerginc 2Y12 receptor agoists
  • receptors
  • thrombin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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