Abstract
Cordycepin (3'-deoxyadenosine), which comes from Cordyceps militaris, the Chinese medicinal fungal genus Cordyceps, is known to have anti-tumour activity. In this study, we investigated the novel effect of cordycepin on human platelet aggregation that was induced by U46619, a thromboxane A(2) (TXA(2)) analogue. TXA(2) is an aggregation-inducing autacoidal molecule that is produced in various agonist-activated platelets. Cordycepin completely inhibited U46619-induced platelet aggregation and simultaneously reduced cytosolic free Ca(2+) ([Ca(2+)](i)), which was increased by U46619 (5 microM) up to 66%. Furthermore, the U46619-stimulated phosphorylation of Ca(2+)-dependent proteins (20 kDa of a myosin light chain and 47 kDa of pleckstrin) was strongly inhibited by cordycepin. These results suggest that cordycepin may have a beneficial effect on autacoidal TXA(2)-mediated thrombotic diseases by inhibiting TXA(2)-induced platelet aggregation via suppression of the Ca(2+) level.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology*
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Blood Proteins / chemistry
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Blood Proteins / metabolism
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Calcium / antagonists & inhibitors
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Calcium / metabolism
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Calcium Chloride / pharmacology
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Calcium Signaling / drug effects
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Deoxyadenosines / chemistry
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Deoxyadenosines / pharmacology*
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Dose-Response Relationship, Drug
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Humans
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Medicine, Chinese Traditional
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Molecular Structure
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Myosin Light Chains / metabolism
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Phosphoproteins / chemistry
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Phosphoproteins / metabolism
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Phosphorus Radioisotopes
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Phosphorylation / drug effects
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Platelet Aggregation / drug effects*
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Platelet Aggregation Inhibitors / chemistry
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Platelet Aggregation Inhibitors / pharmacology*
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Thromboxane A2 / analogs & derivatives
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Thromboxane A2 / pharmacology
Substances
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Antineoplastic Agents
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Blood Proteins
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Deoxyadenosines
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Myosin Light Chains
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Phosphoproteins
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Phosphorus Radioisotopes
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Platelet Aggregation Inhibitors
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platelet protein P47
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Thromboxane A2
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15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
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cordycepin
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Calcium Chloride
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Calcium