The activation of platelets by thrombin: a model for activation by high and moderate affinity receptor pathways
Jamieson, G.A.
Progress in Clinical and Biological Research 283: 137-158
1988
ISSN/ISBN: 0361-7742 PMID: 2850570 Document Number: 3296
Despite sustained efforts in numerous laboratories, major questions regarding the interaction of thrombin with platelets have remained unresolved. Among these unanswered questions have been: (i) What is the relationship between the observed equilibrium binding of thrombin and its ability to activate platelets? (ii) What is the platelet receptor for thrombin and what are the roles of platelet components such as GPIb, GPV and protease nexin in this activation? (iii) Can a satisfactory model be constructed to describe the mechanism of thrombin-induced platelet activation? Thrombin is the only one of the coagulant serine proteases that activates platelets and it causes activation at very low thrombin concentrations, below 1 nM (100 milliunits/ml). Even at these low concentrations platelet response is stronger than is the case with other agonists such as ADP or collagen. When stimulated by thrombin at these low concentrations, platelets undergo shape change, secretion from dense granules, from α-granules and from lysosomes, and membrane changes occur that lead to platelet aggregation. These physiological changes are accompanied by biochemical changes involving Ca++ translocation, prostanoid synthesis, phosphoinositide metabolism and protein phosphorylation: several of these changes are discussed in detail elsewhere in this volume.
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