Abstract
Platelets respond to low levels of agonists such as collagen or thrombin with primary signals that, although small, are functionally significant because they are amplified by autocrine and paracrine pathways such as the secretion of ADP and ATP from the dense granules. An important mediator of the action of low-dose collagen, especially, which is not dependent on granule secretion, is thromboxane A2, a prostanoid that is a potent platelet agonist in its own right, binding to G-protein-linked receptors on the cell surface to stimulate calcium signals via phospholipase Cβ. The precursor of the prostanoids is arachidonic acid (AA), liberated from platelet membrane lipids by the action of phospholipase A2. AA is processed in two stages by cyclooxygenase to yield prostaglandin (PG) H2. This process is aspirin-sensitive, as the drug irreversibly acetylates and inhibits cyclooxygenase, providing the basis for the old and effective antithrombotic use for aspirin, which itself underscores the involvement of collagen in arterial thrombosis. Thromboxane synthase then consumes a proportion of PGH2 to generate thromboxane (Tx) A2. Other products of platelet arachidonate metabolism include PGD2, which exercises an inhibitory role on platelet function as a consequence of its capacity to activate adenylate cyclase, like its homolog, PGI2 (prostacyclin). PGI2 in circulation, however, is largely produced by the vascular endothelial cells rather than the platelets.
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Farndale, R.W., Hargreaves, P.G., Dietrich, J.L., Keogh, R.J. (2004). Measurement of Platelet Arachidonic Acid Metabolism. In: Gibbins, J.M., Mahaut-Smith, M.P. (eds) Platelets and Megakaryocytes. Methods In Molecular Biology™, vol 272. Humana Press. https://doi.org/10.1385/1-59259-782-3:121
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DOI: https://doi.org/10.1385/1-59259-782-3:121
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