About: Aspirin Inhibition of Platelet Activation Pathway

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Attributes	Values
rdf:type	Class
rdfs:label	Aspirin Inhibition of Platelet Activation Pathway
rdfs:subClassOf	Drug Pathway
Semantic_Type	Functional Concept
Preferred_Name	Aspirin Inhibition of Platelet Activation Pathway
UMLS_CUI	C1516047
BioCarta_ID	h_sppaPathway
ALT_DEFINITION	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.BIOCARTA
Legacy_Concept_Name	Aspirin_Inhibition_of_Platelet_Activation_Pathway
FULL_SYN	Aspirin Inhibition of Platelet Activation PathwayPTNCI Aspirin Blocks Signaling Pathway Involved in Platelet ActivationPTBIOCARTA
code	C39235
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