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G-protein-coupled receptors signaling pathways in new antiplatelet drug development.

Publication ,  Journal Article
Gurbel, PA; Kuliopulos, A; Tantry, US
Published in: Arterioscler Thromb Vasc Biol
March 2015

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.

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Published In

Arterioscler Thromb Vasc Biol

DOI

EISSN

1524-4636

Publication Date

March 2015

Volume

35

Issue

3

Start / End Page

500 / 512

Location

United States

Related Subject Headings

  • Thrombosis
  • Signal Transduction
  • Receptors, Purinergic P2Y12
  • Receptors, Proteinase-Activated
  • Receptors, G-Protein-Coupled
  • Purinergic P2Y Receptor Antagonists
  • Platelet Aggregation Inhibitors
  • Molecular Targeted Therapy
  • Humans
  • Drug Design
 

Citation

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Gurbel, P. A., Kuliopulos, A., & Tantry, U. S. (2015). G-protein-coupled receptors signaling pathways in new antiplatelet drug development. Arterioscler Thromb Vasc Biol, 35(3), 500–512. https://doi.org/10.1161/ATVBAHA.114.303412
Gurbel, Paul A., Athan Kuliopulos, and Udaya S. Tantry. “G-protein-coupled receptors signaling pathways in new antiplatelet drug development.Arterioscler Thromb Vasc Biol 35, no. 3 (March 2015): 500–512. https://doi.org/10.1161/ATVBAHA.114.303412.
Gurbel PA, Kuliopulos A, Tantry US. G-protein-coupled receptors signaling pathways in new antiplatelet drug development. Arterioscler Thromb Vasc Biol. 2015 Mar;35(3):500–12.
Gurbel, Paul A., et al. “G-protein-coupled receptors signaling pathways in new antiplatelet drug development.Arterioscler Thromb Vasc Biol, vol. 35, no. 3, Mar. 2015, pp. 500–12. Pubmed, doi:10.1161/ATVBAHA.114.303412.
Gurbel PA, Kuliopulos A, Tantry US. G-protein-coupled receptors signaling pathways in new antiplatelet drug development. Arterioscler Thromb Vasc Biol. 2015 Mar;35(3):500–512.

Published In

Arterioscler Thromb Vasc Biol

DOI

EISSN

1524-4636

Publication Date

March 2015

Volume

35

Issue

3

Start / End Page

500 / 512

Location

United States

Related Subject Headings

  • Thrombosis
  • Signal Transduction
  • Receptors, Purinergic P2Y12
  • Receptors, Proteinase-Activated
  • Receptors, G-Protein-Coupled
  • Purinergic P2Y Receptor Antagonists
  • Platelet Aggregation Inhibitors
  • Molecular Targeted Therapy
  • Humans
  • Drug Design