Cordycepin (3'-deoxyadenosine) inhibits human platelet aggregation induced by U46619, a TXA2 analogue.
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.
Cho
Hyun Jeong
HJ
Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, Regional Research Center, Inje University, Gimhae, Gyungnam 621-749, Korea.
Cho
Jae Youl
JY
Rhee
Man Hee
MH
Lim
Chang Ryul
CR
Park
Hwa Jin
HJ
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001798:Blood Proteins / Q000737:chemistry / Q000378:metabolism; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism; D002122:Calcium Chloride / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D003839:Deoxyadenosines / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008516:Medicine, Chinese Traditional; D015394:Molecular Structure; D018994:Myosin Light Chains / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism; D010761:Phosphorus Radioisotopes; D010766:Phosphorylation / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology
D000970:Antineoplastic Agents; D001798:Blood Proteins; D003839:Deoxyadenosines; D018994:Myosin Light Chains; D010750:Phosphoproteins; D010761:Phosphorus Radioisotopes; D010975:Platelet Aggregation Inhibitors; C039077:platelet protein P47; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C058120:cordycepin; D002122:Calcium Chloride; D002118:Calcium