Introduction

The interaction of proteolytically-active a-thrombin with platelets and other cells of the vasculature, such as endothelial cells and smooth muscle cells, plays a major role in both normal hemostasis and atherosclerosis.1,2 Despite extensive studies in numerous laboratories extending back over thirty years, major questions regarding the mechanism of these interactions remain unresolved. Furthermore, since thrombin can also induce chemotaxis and adhesion of inflammatory cells, and fibroblast mitogenesis, the importance of elucidating the nature of its receptor, or receptors, extends far beyond its role in platelet activation. However, this review will be restricted mainly to considerations of thrombin receptors in human platelets.

The interaction of thrombin with platelets causes increases in cytoplasmic Ca2+, shape change and the conversion of prothrombin to thrombin via the prothrombinase complex leading to further platelet activation, aggregation and secretion. The concentration of free a-thrombin in plasma following physiological activation has been determined to be in the range of 0.5-2nM due to

The authors have collaborated for many years in studies on platelet activating receptors, including not only receptors for a-thrombin but also those for collagen (CD36 and GPVI, laminin (67kOA), and adenosine diphosphate.

the effects of thrombomodulin, antithrombin III and other factors.3,4 In vitro, a-thrombin is one of the most potent known platelet agonists and can cause platelet activation at thrombin concentrations in the picomolar range. Thus, the high a-thrombin concentrations used in some studies, sometimes as high as lOU/ml or lOOnM, could introduce artifacts unrelated to the activation process. Moreover, the a-thrombin used should have a specific activity of at least 3000U/mg since thrombin degradation products such as P- and y-thrombins in preparations of lower purity would not be detectable since they would not clot fibrinogen but would still be capable of causing platelet activation.

0 0

Post a comment