Inhibitory Effects of Cordycepin on Platelet ActivationviaRegulation of Cyclic Adenosine Monophosphate-downstream Pathway

Abstract

Platelet activation is essential at the sites of vascular injury, which leads to hemostasis through adhesion, aggregation, and secretion process. However, potent and continuous platelet activation may be an important reason of circulatory disorders. Therefore, proper regulation of platelet activation may be an effective treatment for vascular diseases. In this research, inhibitory effects of cordycepin (3'-deoxyadenosine) on platelet activation were determined. As the results, cordycepin increased cAMP and cGMP, which are intracellular Ca 2+ -antagonists. In addition, cordycepin reduced collagenelevated [Ca 2+ ] i mobilization, which was increased by a cAMP-dependent protein kinase (PKA) inhibitor (Rp-8-BrcAMPS), but not a cGMP-protein kinase (PKG) inhibitor ) phosphorylation was inhibited by Rp-8-Br-cAMPS, but was not inhibited by Rp-8-Br-cGMPS, and cordycepin inhibited collagen-induced fibrinogen binding to αIIb/β 3 , which was increased by Rp-8-Br-cAMPS, but was not inhibited by Rp-8-Br-cGMPS. These results suggest that the inhibition of αIIb/β 3 activation is caused by the cAMP/A-kinase-dependent VASP (Ser 157 ) phosphorylation. In conclusion, these results demonstrate that inhibitory effects of cordycepin on platelet activation were due to inhibition of [Ca 2+ ] i mobilization through cAMP-dependent IP 3 RI (Ser 1756 ) phosphorylation and suppression of αIIb/β 3 activation through cAMP-dependent VASP (Ser 157 ) phosphorylation. These results strongly indicated that cordycepin might have therapeutic or preventive potential for platelet activation-mediated disorders including thrombosis, atherosclerosis, myocardial infarction, or cardiovascular disease.