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Mechanisms involved in the antiplatelet activity of ketamine in human platelets

  • Original Paper
  • Published:
Journal of Biomedical Science

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.

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Authors and Affiliations

  1. Department of Anesthesiology, Shin Kong Wu Ho-Su Memorial Hospital, China

    Yi Chang & Gong-Jhe Wu

  2. Department of Anesthesiology, Taipei Medical University, Taipei, Taiwan, ROC

    Ta-Liang Chen

  3. Department of Pharmacology, Taipei Medical University, Taipei, Taiwan, ROC

    George Hsiao, Duen-Suey Chou &  Joen-Rong Sheu

  4. Graduate Institute of Medical Sciences, Taipei Medical University, No. 250 Wu-Hsing Street, 110, Taipei, Taiwan (ROC)

    Yi Chang, Ming-Yi Shen, Kuan-Hung Lin, Chien-Huang Lin &  Joen-Rong Sheu

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  1. Yi Chang
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Chang, Y., Chen, TL., Wu, GJ. et al. Mechanisms involved in the antiplatelet activity of ketamine in human platelets. J Biomed Sci 11, 764–772 (2004). https://doi.org/10.1007/BF02254361

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  • DOI: https://doi.org/10.1007/BF02254361

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