Two distinct mechanisms of inhibition of platelets aggregation by acetylsalicylic acid.
The von Willebrand Factor-Ristocetin adduct activates Platelets aggregation and secretion. Acetylsalicylic acid inhibits Platelets activation by two distinct mechanisms indicating that the adduct activates Platelets by triggering at least two distinct intraplatelet metabolic pathways. The first starts from the activation of Phospholipase A-2 that produces Arachidonic acid, which, in turn, undergoes the metabolic pathway leading to Thromboxane A-2; this pathway can be blocked by the intraplatelet Acetylsalicylic acid by irreversible inactivation of Cyclooxygenase but it is insensitive to the extra-platelet Acetylsalicylic acid. The second pathway is triggered by intact von Willebrand Factor, but not by the Acetylsalicylic acid-treated one; it is insensitive to intraplatelet Acetylsalicylic acid and therefore unrelated to the Arachidonic acid metabolism.
Ferri
A
A
Department of Biochemistry and Molecular Biology, University of Ferrara, Italy.
Calza
R
R
Pellegrini
A
A
Cattani
L
L
D016718:Arachidonic Acid / Q000096:biosynthesis; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D010741:Phospholipases A / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D012310:Ristocetin / Q000494:pharmacology; D013928:Thromboxane A2 / Q000097:blood; D014841:von Willebrand Factor / Q000378:metabolism
D010975:Platelet Aggregation Inhibitors; D014841:von Willebrand Factor; D012310:Ristocetin; D016718:Arachidonic Acid; D013928:Thromboxane A2; D010741:Phospholipases A; D001241:Aspirin