Summary
A variety of agonists, when added to human platelets, induce phosphoinositide turnover mediated by phospholipase C. Among such agonists are thrombin, collagen, the \(C{{a}^{{{{2}^{ + }}}}}\) ionophores A23187 and ionomycin, prostaglandin H2/thromboxane A2 (PGH2/TXA2) and a stable analogue, U46619. Secretion of stored substances, including ADP, accompanies phosphoinositide turnover Stimulation of platelets by thrombin, collagen, and \(C{{a}^{{{{2}^{ + }}}}}\) ionophores also results in the liberation of arachidonic acid, which is converted by platelet cyclooxygenase to PGH2/TXA2. However, PGH2/TXA2 and U46619 are themselves poor inducers of arachidonic acid release.
Thrombin stimulates a phospholipase C-mediated transient accumulation of diacylglycerol which is not inhibited by either blocking PGH2/TXA2 formation or removing ADP. Collagen-induced formation of diacylglycerol is partially dependent upon TXA2/PGH2 and ADP, whereas activation of phospholipase C by ionophores is completely dependent upon these species. In contrast, making PGH2/TXA2 and ADP unavailable does not impair the elevation of cytoplasmic Ca2+ (monitored by Quin 2) and activation of phospholipase A2 caused by ionophores. Thus, Ca2+ ionophores stimulate phospholipase A2, but activate phospholipase C only indirectly, via PGH2/TXA2 and ADP effects. We conclude that phospholipase C is not activated by a Ca2+ flux in the platelet, and suggest that stimulation of phospholipase C is contingent upon a receptor-coupled event.
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Rittenhouse, S.E. (1985). The Mobilization of Arachidonate and Metabolism of Phosphoinositides in Stimulated Human Platelets. In: Bleasdale, J.E., Eichberg, J., Hauser, G. (eds) Inositol and Phosphoinositides. Experimental Biology and Medicine, vol 6. Humana Press. https://doi.org/10.1007/978-1-4612-5184-2_30
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DOI: https://doi.org/10.1007/978-1-4612-5184-2_30
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