Original Paper

Journal of Biomedical Science

, Volume 11, Issue 6, pp 764-772

Mechanisms involved in the antiplatelet activity of ketamine in human platelets

  • Yi ChangAffiliated withDepartment of Anesthesiology, Shin Kong Wu Ho-Su Memorial HospitalGraduate Institute of Medical Sciences, Taipei Medical University
  • , Ta-Liang ChenAffiliated withDepartment of Anesthesiology, Taipei Medical University, Taipei
  • , Gong-Jhe WuAffiliated withDepartment of Anesthesiology, Shin Kong Wu Ho-Su Memorial Hospital
  • , George HsiaoAffiliated withDepartment of Pharmacology, Taipei Medical University, Taipei
  • , Ming-Yi ShenAffiliated withGraduate Institute of Medical Sciences, Taipei Medical University
  • , Kuan-Hung LinAffiliated withGraduate Institute of Medical Sciences, Taipei Medical University
  • , Duen-Suey ChouAffiliated withDepartment of Pharmacology, Taipei Medical University, Taipei
  • , Chien-Huang LinAffiliated withGraduate Institute of Medical Sciences, Taipei Medical University
  • , Joen-Rong SheuAffiliated withDepartment of Pharmacology, Taipei Medical University, TaipeiGraduate Institute of Medical Sciences, Taipei Medical University

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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

Ketamine Phospholipase C Platelet aggregation Protein kinase C Thromboxane A2