TY - JOUR
T1 - Cordycepin (3′-deoxyadenosine) inhibits human platelet aggregation in a cyclic AMP- and cyclic GMP-dependent manner
AU - Cho, Hyun Jeong
AU - Cho, Jae Youl
AU - Rhee, Man Hee
AU - Park, Hwa Jin
PY - 2007/3/8
Y1 - 2007/3/8
N2 - 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 CaCl2. Of two aggregation-inducing molecules, cytosolic free Ca2+ ([Ca2+]i) and thromboxane A2 (TXA2), cordycepin (500 μM) blocked the up-regulation of [Ca2+]i, by up to 74%, but suppressed TXA2 production by 46%. Subsequently, Ca2+-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-γ2 (PLC-γ2) (assessed by the phosphotyrosine level) and the formation of inositol 1,4,5-trisphosphate (IP3), 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 [Ca2+]i and the elevation of cAMP/cGMP production.
AB - 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 CaCl2. Of two aggregation-inducing molecules, cytosolic free Ca2+ ([Ca2+]i) and thromboxane A2 (TXA2), cordycepin (500 μM) blocked the up-regulation of [Ca2+]i, by up to 74%, but suppressed TXA2 production by 46%. Subsequently, Ca2+-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-γ2 (PLC-γ2) (assessed by the phosphotyrosine level) and the formation of inositol 1,4,5-trisphosphate (IP3), 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 [Ca2+]i and the elevation of cAMP/cGMP production.
KW - cAMP
KW - cGMP
KW - Cordycepin
KW - Human platelet aggregation
UR - http://www.scopus.com/inward/record.url?scp=33847374642&partnerID=8YFLogxK
U2 - 10.1016/j.ejphar.2006.11.073
DO - 10.1016/j.ejphar.2006.11.073
M3 - Article
C2 - 17229422
AN - SCOPUS:33847374642
SN - 0014-2999
VL - 558
SP - 43
EP - 51
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 1-3
ER -