Journal of Biomedical Science

, Volume 11, Issue 6, pp 764–772

Mechanisms involved in the antiplatelet activity of ketamine in human platelets

  • Yi Chang
  • Ta-Liang Chen
  • Gong-Jhe Wu
  • George Hsiao
  • Ming-Yi Shen
  • Kuan-Hung Lin
  • Duen-Suey Chou
  • Chien-Huang Lin
  • Joen-Rong Sheu
Original Paper

DOI: 10.1007/BF02254361

Cite this article as:
Chang, Y., Chen, TL., Wu, GJ. et al. J Biomed Sci (2004) 11: 764. doi:10.1007/BF02254361

Abstract

The aim of this study was to systematically examine the inhibitory mechanisms of ketamine in platelet aggregation. In this study, ketamine concentration-dependently (100–350 µM) inhibited platelet aggregation both in washed human platelet suspensions and platelet-rich plasma stimulated by agonists. Ketamine inhibited phosphoinositide breakdown and intracellular Ca2+ mobilization in human platelets stimulated by collagen. Ketamine (200 and 350 µM) significantly inhibited thromboxane (Tx) A2 formation stimulated by collagen. Moreover, ketamine (200 and 350 µM) increased the fluorescence of platelet membranes tagged with diphenylhexatriene. Rapid phosphorylation of a platelet protein ofMr 47,000 (P47), a marker of protein kinase C activation, was triggered by phorbol-12,13-dibutyrate (100 nM). This phosphorylation was markedly inhibited by ketamine (350 µM). These results indicate that the antiplatelet activity of ketamine may be involved in the following pathways. Ketamine may change platelet membrane fluidity, with a resultant influence on activation of phospholipase C, and subsequent inhibition of phosphoinositide breakdown and phosphorylation of P47, thereby leading to inhibition of intracellular Ca2+ mobilization and TxA2 formation, ultimately resulting in inhibition of platelet aggregation.

Key Words

KetaminePhospholipase CPlatelet aggregationProtein kinase CThromboxane A2

Copyright information

© National Science Council 2004

Authors and Affiliations

  • Yi Chang
    • 1
    • 4
  • Ta-Liang Chen
    • 2
  • Gong-Jhe Wu
    • 1
  • George Hsiao
    • 3
  • Ming-Yi Shen
    • 4
  • Kuan-Hung Lin
    • 4
  • Duen-Suey Chou
    • 3
  • Chien-Huang Lin
    • 4
  • Joen-Rong Sheu
    • 3
    • 4
  1. 1.Department of AnesthesiologyShin Kong Wu Ho-Su Memorial HospitalChina
  2. 2.Department of AnesthesiologyTaipei Medical University, TaipeiTaiwanROC
  3. 3.Department of PharmacologyTaipei Medical University, TaipeiTaiwanROC
  4. 4.Graduate Institute of Medical SciencesTaipei Medical UniversityTaipeiTaiwan (ROC)