Aspirin Inhibition of Platelet Activation Pathway

Preferred Label : Aspirin Inhibition of Platelet Activation Pathway;

NCIt related terms : Aspirin Blocks Signaling Pathway Involved in Platelet Activation;

Alternative definition : BIOCARTA: Activation of the protease-activated GPCRs in platelets contributes to platelet activation in clotting. The protease-activated receptors PAR1 and PAR4 are cleaved by the protease thrombin, releasing a tethered peptide ligand that activates the receptor and triggers intracellular calcium release. Platelets from mice lacking the PAR4 gene are not activated by thrombin and are impaired in clotting, supporting the importance of thrombin signaling through PAR4 in clotting. Human platelets express both PAR1 and PAR4, with PAR1 playing a more dominant role in clotting in humans. Calcium release induced by PARs activates PKC, modulating integrin alpha IIB beta 3 (glycoprotein IIb/IIIa) and opening integrin ligand binding sites to contribute to platelet aggregation. Intracellular calcium increases induced by thrombin activate phospholipase A2, liberating arachidonic acid, the first step in prostaglandin and thromboxane biosynthesis. Ras/Map kinase activation by the PAR receptors also activates phospholipase A2. The activation of PAR-induced platelet aggregation is inhibited by aspirin, indicating that thromboxane production induced by PAR signaling contributes to platelet activation. Arachidonic acid is converted to the prostaglandin PGG2 by the enzyme Cox-1 in platelets, and Cox-1 is inhibited by aspirin, reducing thromboxane A2 production by platelets. Thromboxane is a potent vasoconstrictor and platelet activator, so inhibition of Cox-1 in platelets by aspirin may explain some of the cardioprotective actions of aspirin. (This definition may be outdated - see the DesignNote.);

NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA Definition might be outdated or inaccurate. Please see the Terms and Conditions for Use at http://www.biocarta.com/.;

Biocarta ID : h_sppaPathway;

Details

Origin ID

C39235;

UMLS CUI

C1516047;

Semantic type(s)
- Conceptual Entity [UMLS semantic type]
has_gene_product_element
- Cytosolic Phospholipase A2 [NCIt concept]
- Dual Specificity Mitogen-Activated Protein Kinase Kinase 1 [NCIt concept]
- Focal Adhesion Kinase 1 [NCIt concept]
- GTPase HRas [NCIt concept]
- Guanine Nucleotide-Binding Protein G(i) Subunit Alpha-1 [NCIt concept]
- Mitogen-Activated Protein Kinase 1 [NCIt concept]
- Mitogen-Activated Protein Kinase 3 [NCIt concept]
- Prostaglandin G/H Synthase 1 [NCIt concept]
- Protease-Activated Receptor 1 [NCIt concept]
- Protein Kinase C Alpha Type [NCIt concept]
- Proteinase-Activated Receptor 4 [NCIt concept]
- Prothrombin [NCIt concept]
- Proto-Oncogene Tyrosine-Protein Kinase Src [NCIt concept]
- RAF Proto-Oncogene Serine/Threonine-Protein Kinase [NCIt concept]
- Tyrosine-Protein Kinase SYK [NCIt concept]
pathway_has_gene_element
- F2 wt Allele [NCIt concept]
- F2R wt Allele [NCIt concept]
- F2RL3 wt Allele [NCIt concept]
- GNAI1 wt Allele [NCIt concept]
- HRAS wt Allele [NCIt concept]
- MAP2K1 wt Allele [NCIt concept]
- MAPK1 wt Allele [NCIt concept]
- MAPK3 wt Allele [NCIt concept]
- PLA2G4A wt Allele [NCIt concept]
- PRKCA wt Allele [NCIt concept]
- PTGS1 wt Allele [NCIt concept]
- PTK2 wt Allele [NCIt concept]
- RAF1 wt Allele [NCIt concept]
- SRC wt Allele [NCIt concept]
- SYK wt Allele [NCIt concept]

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