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Synergistic responses in human platelets. Comparison between aggregation, secretion and cytosolic Ca2+ concentration
European Journal of Biochemistry
|December 1, 1986
Summary
Platelet aggregation studies reveal that aggregometers may overestimate synergistic responses. However, adrenaline enhances calcium (Ca2+) influx and serotonin secretion in aspirin-treated human platelets, suggesting alpha 2-adrenoceptor modulation of signaling pathways.
Area of Science:
- Biochemistry
- Pharmacology
- Hematology
Background:
- Platelet aggregation is crucial for hemostasis and thrombosis.
- Agonist interactions in platelet function are complex and can be synergistic.
- Previous studies suggested synergistic interactions between various agonists in platelet aggregation.
Purpose of the Study:
- To investigate the synergistic interactions of ADP, adrenaline, 5-hydroxytryptamine (5HT), and [8-arginine]vasopressin on human platelet aggregation.
- To explore the role of these agonists in cytosolic calcium ([Ca2+]) increase and serotonin secretion.
- To elucidate the mechanism of adrenaline's effect on platelet activation.
Main Methods:
- Human platelet aggregation measured by decrease in single platelets and light transmittance.
- Measurement of cytosolic [Ca2+] using fluorescent indicators.
- Assessment of [3H]5HT secretion.
- Use of manganese (Mn2+) as a probe for Ca2+ influx.
- Platelet treatment with aspirin and various agonists including ADP, adrenaline, 5HT, vasopressin, collagen, U46619, and ionomycin.
Main Results:
- Synergistic platelet aggregation was not observed when measured by single platelet count, contrasting with aggregometer data.
- Significant synergistic increases in cytosolic [Ca2+] were observed with ADP/5HT and ADP/vasopressin pairs.
- Adrenaline significantly enhanced agonist-induced cytosolic [Ca2+] increase and [3H]5HT secretion in a calcium-dependent manner, acting via alpha 2-adrenoceptors.
- Adrenaline's enhancement of Ca2+ influx was confirmed using Mn2+.
- Adrenaline's effects did not involve adenylate cyclase inhibition.
Conclusions:
- Platelet aggregometers may overestimate synergistic responses due to limitations in detecting initial aggregation phases.
- Adrenaline modulates platelet activation, likely through alpha 2-adrenoceptor-mediated effects on receptor-phospholipase-C coupling.
- Adrenaline plays a significant role in enhancing calcium influx and serotonin secretion, contributing to platelet responsiveness.