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Mechanisms of Platelet Activation and Integrin αIIβ3.

Joo SJ - Korean Circ J (2012)

Bottom Line: G protein-mediated signaling pathways, which are initiated by G(q), G(12)/G(13) or G(i), include phospholipase C with calcium signaling, Rho signaling, protein kinase C and phosphatidylinositol 3-kinase.Rap1b, Ca(2+) and diacylglycerol-regulated guanine nucleotide exchange factor I, Rap1-GTP-interacting adaptor molecule, and Akt are important proteins involved in G protein-mediated activation of integrin αIIbβ3.Binding of talin-1 and kindlin-3 to cytoplasmic domains of β3-integrin triggers a conformational change in the extracellular domains that increases its affinity for ligands, such as fibrinogen or von Willebrand factor.

View Article: PubMed Central - PubMed

Affiliation: Cardiology Division, Department of Internal Medicine, Jeju National University Hospital, Jeju, Korea.

ABSTRACT
Platelet aggregation is not only an essential part of hemostasis, but also initiates acute coronary syndrome or ischemic stroke. The precise understanding of the activation mechanism of platelet aggregation is fundamental for the development of more effective agents against platelet aggregation. Adenosine diphosphate, thrombin, and thromboxane A(2) activate platelet integrin αIIbβ3 through G protein-coupled receptors. G protein-mediated signaling pathways, which are initiated by G(q), G(12)/G(13) or G(i), include phospholipase C with calcium signaling, Rho signaling, protein kinase C and phosphatidylinositol 3-kinase. Rap1b, Ca(2+) and diacylglycerol-regulated guanine nucleotide exchange factor I, Rap1-GTP-interacting adaptor molecule, and Akt are important proteins involved in G protein-mediated activation of integrin αIIbβ3. Binding of talin-1 and kindlin-3 to cytoplasmic domains of β3-integrin triggers a conformational change in the extracellular domains that increases its affinity for ligands, such as fibrinogen or von Willebrand factor. Fibrinogens act as bridges between adjacent platelets to generate a platelet aggregate.

No MeSH data available.


Related in: MedlinePlus

Mechanism of action of platelet glycoprotein (GP) IIb/IIIa blockers. Activated GP IIb/IIIa binds to fibrinogen at high affinity. Fibrinogen acts as a bridge between adjacent platelets, forming firm platelet aggregates. GP IIb/IIIa receptor antagonists inhibit fibrinogen binding to the receptors.
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Figure 5: Mechanism of action of platelet glycoprotein (GP) IIb/IIIa blockers. Activated GP IIb/IIIa binds to fibrinogen at high affinity. Fibrinogen acts as a bridge between adjacent platelets, forming firm platelet aggregates. GP IIb/IIIa receptor antagonists inhibit fibrinogen binding to the receptors.

Mentions: GP IIb/IIIa receptor blockers inhibit fibrinogen binding to the receptors, resulting in the suppression of platelets aggregation (Fig. 5). Abciximab, chimerized monoclonal antibody to integrin αIIbβ3 (c7E3) to reduce immunogenicity, was the first GPIIb/IIIa receptor blocker to be widely used in humans. The peptides recognized by integrin αIIbβ3 were used in drug development. Eptifibatide contains the amino acid sequence, Lys-Gly-Asp (KGD) within a disulphide ring. Tirofiban is a synthetic, non-peptide inhibitor based on RGD sequence.17)18)


Mechanisms of Platelet Activation and Integrin αIIβ3.

Joo SJ - Korean Circ J (2012)

Mechanism of action of platelet glycoprotein (GP) IIb/IIIa blockers. Activated GP IIb/IIIa binds to fibrinogen at high affinity. Fibrinogen acts as a bridge between adjacent platelets, forming firm platelet aggregates. GP IIb/IIIa receptor antagonists inhibit fibrinogen binding to the receptors.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3369959&req=5

Figure 5: Mechanism of action of platelet glycoprotein (GP) IIb/IIIa blockers. Activated GP IIb/IIIa binds to fibrinogen at high affinity. Fibrinogen acts as a bridge between adjacent platelets, forming firm platelet aggregates. GP IIb/IIIa receptor antagonists inhibit fibrinogen binding to the receptors.
Mentions: GP IIb/IIIa receptor blockers inhibit fibrinogen binding to the receptors, resulting in the suppression of platelets aggregation (Fig. 5). Abciximab, chimerized monoclonal antibody to integrin αIIbβ3 (c7E3) to reduce immunogenicity, was the first GPIIb/IIIa receptor blocker to be widely used in humans. The peptides recognized by integrin αIIbβ3 were used in drug development. Eptifibatide contains the amino acid sequence, Lys-Gly-Asp (KGD) within a disulphide ring. Tirofiban is a synthetic, non-peptide inhibitor based on RGD sequence.17)18)

Bottom Line: G protein-mediated signaling pathways, which are initiated by G(q), G(12)/G(13) or G(i), include phospholipase C with calcium signaling, Rho signaling, protein kinase C and phosphatidylinositol 3-kinase.Rap1b, Ca(2+) and diacylglycerol-regulated guanine nucleotide exchange factor I, Rap1-GTP-interacting adaptor molecule, and Akt are important proteins involved in G protein-mediated activation of integrin αIIbβ3.Binding of talin-1 and kindlin-3 to cytoplasmic domains of β3-integrin triggers a conformational change in the extracellular domains that increases its affinity for ligands, such as fibrinogen or von Willebrand factor.

View Article: PubMed Central - PubMed

Affiliation: Cardiology Division, Department of Internal Medicine, Jeju National University Hospital, Jeju, Korea.

ABSTRACT
Platelet aggregation is not only an essential part of hemostasis, but also initiates acute coronary syndrome or ischemic stroke. The precise understanding of the activation mechanism of platelet aggregation is fundamental for the development of more effective agents against platelet aggregation. Adenosine diphosphate, thrombin, and thromboxane A(2) activate platelet integrin αIIbβ3 through G protein-coupled receptors. G protein-mediated signaling pathways, which are initiated by G(q), G(12)/G(13) or G(i), include phospholipase C with calcium signaling, Rho signaling, protein kinase C and phosphatidylinositol 3-kinase. Rap1b, Ca(2+) and diacylglycerol-regulated guanine nucleotide exchange factor I, Rap1-GTP-interacting adaptor molecule, and Akt are important proteins involved in G protein-mediated activation of integrin αIIbβ3. Binding of talin-1 and kindlin-3 to cytoplasmic domains of β3-integrin triggers a conformational change in the extracellular domains that increases its affinity for ligands, such as fibrinogen or von Willebrand factor. Fibrinogens act as bridges between adjacent platelets to generate a platelet aggregate.

No MeSH data available.


Related in: MedlinePlus