• Biomedical Science Letters
• /
• v.10 no.1
• /
• pp.1-8
• /
• 2004

Cordycepin separated from Cordyceps militaris is a major physiologic active component in Cordyceps militaris. The platelet aggregation is stimulated by $Ca^{2+}$, which is either mobilized from intracellular endoplasmic reticulum or transported from extracellular space. cGMP antagonizes the actions of $Ca^{2+}$. Based on these facts, we have investigated the effects of cordycepin on the mobilization of $Ca^{2+}$ and the production of cGMP on collagen ($10\mu$g/ml)-induced human platelet aggregation. Cordycepin potently stimulated the human platelet aggregation induced by collagen ($10\mu$g/ml) in a dose-dependent manner. Cordycepin (500 $\mu$M) inhibited also the collagen-induced human platelet aggregation in the presence both 1 mM and 2 mM of $CaCl_2$. These are in accord with the results that cordycepin inhibited the $Ca^{2+}$- influx on collagen-induced human platelet aggregation. These results suggest that cordycepin decrease the intracellular $Ca^{2+}$ concentration to inhibit collagen-induced human platelet aggregation. Besides, cordycepin increased the level of cGMP on collagen-induced human platelet aggregation. This result is related with the decrease of intracellular $Ca^{2+}$ concentration, because cGMP inhibits the mobilization of $Ca^{2+}$. In addition, cordycepin inhibited the human platelet aggregation induced by LY -83583, inhibitor of guanylate cyclase. This result suggested that cordycepin inhibit the platelet aggregation by stimulating the activity of guanylate cyclase. In conclusion, we demonstrated that cordycepin might have the antiplatelet function by inhibiting $Ca^{2+}$-mobilization via the stimulation of the production of cGMP.

• The Korean Journal of Pharmacology
• /
• v.31 no.3
• /
• pp.299-311
• /
• 1995

Platelets resemble monoaminergic neurons in several respects, i.e. the uptake of 5-HT and its inhibition, the subcellular storage and release of 5-HT, and the metabolism of aromatic amines brought about by monoamine oxidase. And the 5-HT content of rabbit platelets is well known to be about 40 times higher than that of human platelets. Therefore, this study was carried out to investigate the influences of amitriptyline (AMT) and sertraline (SRT) on the aggregation, contents of signaling second messengers, and protein phosphorylations of rabbit platelets in response to thrombin, 0.25 unit/ml, comparing with those of chlorpromazine (CPZ). Thrombin-induced aggregation was inhibited by SRT $(IC50:4.37{\times}10^{-5}\;M)$, CPZ $(IC50:5.76{\times}10^{-5}\;M)$, and AMT $(IC50:1.15{\times}10^{-4}\;M)$, respectively, and the aggregation by A23187 $(1.0\;{\mu}M)$ or PMA (320 nM) was also inhibited by SRT, CPZ, and AMT. AMT, SRT, and CPZ had little affects on basal contents of platelet $TXB_2$ and $PGE_2$, but all of them inhibited the thrombin-induced increase of $TXB_2$. Thrombin did not change the platelet contents of cAMP and cGMP. CPZ, AMT, and SRT produced the slight decrease of basal cAMP content, and their effects were not affected by thrombin-treatment. But SRT and AMT moderately increased the basal cGMP content, and the cGMP content of thrombin-stimulated platelets was gradually increased by the pretreatment with SRT, AMT, and CPZ. Particularly, the SRT-dependent increase of the cGMP content was notable. Platelet $Ins(1,4,5)P_3$ content was rapidly increased up to a plateau within 10 sec after thrombin-stimulation, AMT, SRT, and CPZ increased the basal $Ins(1,4,5)P_3$ content, and the thrombin-dependent increase was enhanced by pretreatment with CPZ and AMT, but was blunted by SRT. Platelet $[Ca^{2+}]_i$, was rapidly increased up to a peak level within 20 sec after thrombin-stimulation. The increase of $[Ca^{2+}]_i$ was sisnificantly inhibited by AMT, SRT, and CPZ. Thrombin- or PMA-induced phosphorylations of platelet $41{\sim}43\;kDa$ and 20 kDa proteins were significantly inhibited by AMT, SRT, and CPZ. These results suggest that the antiplatelet activities of AMT and CPZ may be considerably attributed to the inhibition of protein kinase C activity, and the activity of SRT may be associated with the inhibitory effect on the thrombin-induced increase of $Ins(1,4,5)P_3$ and the increasing effect on the cGMP content of ptatelets. Therefore, it seems to be evident that AMT and SRT may produce their antidepressant activity, at least, partly through the inhibition of protein kinase C activity or the increase of resting $Ins(1,4,5)P_3$, content and in case of SRT, to a lesser extent, via the increase of cGMP in the brain.