Cordycepin (3'-deoxyadenosine) inhibits human platelet aggregation induced by U46619, a TXA2 analogue

J Pharm Pharmacol. 2006 Dec;58(12):1677-82. doi: 10.1211/jpp.58.12.0016.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Blood Proteins / chemistry
  • Blood Proteins / metabolism
  • Calcium / antagonists & inhibitors
  • Calcium / metabolism
  • Calcium Chloride / pharmacology
  • Calcium Signaling / drug effects
  • Deoxyadenosines / chemistry
  • Deoxyadenosines / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • Medicine, Chinese Traditional
  • Molecular Structure
  • Myosin Light Chains / metabolism
  • Phosphoproteins / chemistry
  • Phosphoproteins / metabolism
  • Phosphorus Radioisotopes
  • Phosphorylation / drug effects
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / chemistry
  • Platelet Aggregation Inhibitors / pharmacology*
  • Thromboxane A2 / analogs & derivatives
  • Thromboxane A2 / pharmacology

Substances

  • Antineoplastic Agents
  • Blood Proteins
  • Deoxyadenosines
  • Myosin Light Chains
  • Phosphoproteins
  • Phosphorus Radioisotopes
  • Platelet Aggregation Inhibitors
  • platelet protein P47
  • Thromboxane A2
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • cordycepin
  • Calcium Chloride
  • Calcium