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G-protein-coupled receptors as signaling targets for antiplatelet therapy.

Publication ,  Journal Article
Smyth, SS; Woulfe, DS; Weitz, JI; Gachet, C; Conley, PB; Goodman, SG; Roe, MT; Kuliopulos, A; Moliterno, DJ; French, PA; Steinhubl, SR ...
Published in: Arterioscler Thromb Vasc Biol
April 2009

Platelet G protein-coupled receptors (GPCRs) initiate and reinforce platelet activation and thrombus formation. The clinical utility of antagonists of the P2Y(12) receptor for ADP suggests that other GPCRs and their intracellular signaling pathways may represent viable targets for novel antiplatelet agents. For example, thrombin stimulation of platelets is mediated by 2 protease-activated receptors (PARs), PAR-1 and PAR-4. Signaling downstream of PAR-1 or PAR-4 activates phospholipase C and protein kinase C and causes autoamplification by production of thromboxane A(2), release of ADP, and generation of more thrombin. In addition to ADP receptors, thrombin and thromboxane A(2) receptors and their downstream effectors-including phosphoinositol-3 kinase, Rap1b, talin, and kindlin-are promising targets for new antiplatelet agents. The mechanistic rationale and available clinical data for drugs targeting disruption of these signaling pathways are discussed. The identification and development of new agents directed against specific platelet signaling pathways may offer an advantage in preventing thrombotic events while minimizing bleeding risk.

Duke Scholars

Published In

Arterioscler Thromb Vasc Biol

DOI

EISSN

1524-4636

Publication Date

April 2009

Volume

29

Issue

4

Start / End Page

449 / 457

Location

United States

Related Subject Headings

  • Thromboxanes
  • Thrombin
  • Signal Transduction
  • Receptors, Thromboxane
  • Receptors, Thrombin
  • Receptors, Purinergic P2Y12
  • Receptors, Purinergic P2Y1
  • Receptors, G-Protein-Coupled
  • Receptor, PAR-1
  • Purinergic P2 Receptor Antagonists
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Smyth, S. S., Woulfe, D. S., Weitz, J. I., Gachet, C., Conley, P. B., Goodman, S. G., … 2008 Platelet Colloquium Participants, . (2009). G-protein-coupled receptors as signaling targets for antiplatelet therapy. Arterioscler Thromb Vasc Biol, 29(4), 449–457. https://doi.org/10.1161/ATVBAHA.108.176388
Smyth, Susan S., Donna S. Woulfe, Jeffrey I. Weitz, Christian Gachet, Pamela B. Conley, Shaun G. Goodman, Matthew T. Roe, et al. “G-protein-coupled receptors as signaling targets for antiplatelet therapy.Arterioscler Thromb Vasc Biol 29, no. 4 (April 2009): 449–57. https://doi.org/10.1161/ATVBAHA.108.176388.
Smyth SS, Woulfe DS, Weitz JI, Gachet C, Conley PB, Goodman SG, et al. G-protein-coupled receptors as signaling targets for antiplatelet therapy. Arterioscler Thromb Vasc Biol. 2009 Apr;29(4):449–57.
Smyth, Susan S., et al. “G-protein-coupled receptors as signaling targets for antiplatelet therapy.Arterioscler Thromb Vasc Biol, vol. 29, no. 4, Apr. 2009, pp. 449–57. Pubmed, doi:10.1161/ATVBAHA.108.176388.
Smyth SS, Woulfe DS, Weitz JI, Gachet C, Conley PB, Goodman SG, Roe MT, Kuliopulos A, Moliterno DJ, French PA, Steinhubl SR, Becker RC, 2008 Platelet Colloquium Participants. G-protein-coupled receptors as signaling targets for antiplatelet therapy. Arterioscler Thromb Vasc Biol. 2009 Apr;29(4):449–457.

Published In

Arterioscler Thromb Vasc Biol

DOI

EISSN

1524-4636

Publication Date

April 2009

Volume

29

Issue

4

Start / End Page

449 / 457

Location

United States

Related Subject Headings

  • Thromboxanes
  • Thrombin
  • Signal Transduction
  • Receptors, Thromboxane
  • Receptors, Thrombin
  • Receptors, Purinergic P2Y12
  • Receptors, Purinergic P2Y1
  • Receptors, G-Protein-Coupled
  • Receptor, PAR-1
  • Purinergic P2 Receptor Antagonists