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Epinephrine induces a late thromboxane-dependent platelet shape change and enhances synergistically the shape change induced by other platelet agonists

 

作者: BlockmansD.,   DeckmynH.,   De VosR.,   VermylenJ.,  

 

期刊: Platelets  (Taylor Available online 1996)
卷期: Volume 7, issue 1-2  

页码: 35-42

 

ISSN:0953-7104

 

年代: 1996

 

DOI:10.3109/09537109609079507

 

出版商: Taylor&Francis

 

数据来源: Taylor

 

摘要:

Epinephrine is the only physiological platelet activator which induces platelet aggregation without a preceding change in platelet shape. The reason why epinephrine cannot induce this shape change is not known. Electron microscopically, we could show that during the first phase of epinephrine-induced platelet aggregation, the platelet aggregate is composed of discoid platelets, lying in rather loose contact with neighbouring platelets. During the second wave of epinephrine-induced aggregation (this is when thromboxane (TX)A2production has taken place), platelets have completely lost their discoid shape and are very tightly bound. In EDTA-platelet rich plasma (PRP), we could demonstrate a clear synergistic action of epinephrine 10–20μM on the first phase of shape change (disc-to-sphere transformation), induced by low concentrations of arachidonic acid (AA), collagen, adenosine diphosphate (ADP) and platelet activating factor (PAF). In combination with moderate concentrations of AA or collagen, epinephrine induced a clear aggregation-independent secretion of platelet granules, which in the absence of epinephrine, only takes place with higher inducer concentrations. All these synergistic actions could be demonstrated in the aggregometer and electron microscopically. To explain these findings, we hypothesize that the inability of epinephrine to induce a shape change that precedes aggregation is due to slow generation of TXA2which is only formed as a positive feedback mechanism of aggregation. This TXA2will bind to its own receptor and produce a shape change coinciding with the second wave of epinephrine-induced aggregation. Collagen, in contrast, induces very rapid TXA2generation, causing Ca2+mobilization and myosin light chain-phosphorylation, leading to shape change, clearly before aggregation starts.

 

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