Cordycepin (3'-deoxyadenosine) inhibits human platelet aggregation in a cyclic AMP- and cyclic GMP-dependent manner.
Cordycepin (3'-deoxyadenosine) is isolated from Cordyceps militaris, a species of the fungal genus Cordyceps. Cordycepin is an ingredient used in traditional Chinese medicine and is prescribed for various diseases, such as cancer and chronic inflammation. In this study, we investigated the novel effect of cordycepin (3'-deoxyadenosine) on collagen-induced human platelet aggregation. Cordycepin inhibited dose-dependently collagen-induced platelet aggregation in the presence of various concentrations of exogenous CaCl(2). Of two aggregation-inducing molecules, cytosolic free Ca(2+) ([Ca(2+)](i)) and thromboxane A(2) (TXA(2)), cordycepin (500 microM) blocked the up-regulation of [Ca(2+)](i), by up to 74%, but suppressed TXA(2) production by 46%. Subsequently, Ca(2+)-dependent phosphorylation of both 47-kDa and 20-kDa proteins in collagen-treated platelets was potently diminished by cordycepin. However, upstream pathways for producing these two inducers, such as the activation of phospholipase C-gamma2 (PLC-gamma2) (assessed by the phosphotyrosine level) and the formation of inositol 1,4,5-trisphosphate (IP(3)), were not altered by cordycepin. Cordycepin increased the level of second messengers adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) in collagen-stimulated platelets. Whereas the NO-sensitive guanylyl cyclase inhibitor ODQ did not alter the cordycepin-induced up-regulation of cGMP, the adenylyl cyclase inhibitor SQ22536 completely blocked the cAMP enhancement mediated by cordycepin, indicating that cordycepin had different modes of action. Therefore, our data suggest that the inhibitory effect of cordycepin on platelet aggregation might be associated with the down-regulation of [Ca(2+)](i) and the elevation of cAMP/cGMP production.
Cho
Hyun-Jeong
HJ
Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, and Regional Research Center, Inje University, 607, Obang-Dong, Gimhae, Gyungnam, Republic of Korea.
Cho
Jae Youl
JY
Rhee
Man Hee
MH
Park
Hwa-Jin
HJ
D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D006152:Cyclic GMP / Q000502:physiology*; D003839:Deoxyadenosines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051966:Phospholipase C gamma / Q000502:physiology; D010766:Phosphorylation; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000096:biosynthesis
D003839:Deoxyadenosines; D010975:Platelet Aggregation Inhibitors; D013928:Thromboxane A2; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D051966:Phospholipase C gamma; C058120:cordycepin; D006152:Cyclic GMP; D002118:Calcium