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Thapsigargin amplifies the platelet procoagulant response caused by thrombin
E F Smeets1, J W Heemskerk, P Comfurius
1Dept. of Biochemistry, Cardiovascular Research Institute Maastricht, University of Limburg, The Netherlands.
Thrombosis and Haemostasis
|December 20, 1993
Summary
Thrombin and thapsigargin synergistically enhance platelet procoagulant activity. This amplified response, involving microvesicle shedding and altered phosphatidylserine transport, suggests additional factors beyond calcium levels regulate clotting.
Area of Science:
- Hematology
- Biochemistry
- Cell Biology
Background:
- Platelet procoagulant response involves phosphatidylserine exposure, crucial for coagulation complex assembly.
- Extracellular calcium (Ca2+) is essential for platelet procoagulant activity, which varies with agonist type.
Purpose of the Study:
- To investigate the synergistic effect of thapsigargin on thrombin-induced platelet procoagulant activity.
- To elucidate the mechanisms underlying the amplified procoagulant response.
Main Methods:
- Stimulation of human platelets with thrombin and thapsigargin.
- Measurement of platelet procoagulant activity.
- Assessment of microvesicle shedding.
- Analysis of phosphatidylserine transport using fluorescent analogs and aminophospholipid translocase activity.
Main Results:
- Thapsigargin strongly amplified the moderate procoagulant response induced by thrombin.
- Combined agonists increased microvesicle shedding and inhibited phosphatidylserine transport.
- Elevated intracellular calcium ([Ca2+]) contributed to the synergistic effect but was insufficient to fully explain it.
Conclusions:
- The synergistic effect of thapsigargin on thrombin-induced platelet procoagulant activity is partially mediated by increased intracellular calcium.
- Additional factors, beyond intracellular calcium levels, are involved in regulating platelet procoagulant activity.
- Findings support current models of procoagulant activity development and suggest new regulatory mechanisms.