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Interactions of the Alkyl-Ether-Phospholipid, Platelet Activating Factor (PAF) with Platelets, Neural Cells, and the Psychotropic Drugs Triazolobenzodiazepines

  • E. Kornecki
  • R. H. Lenox
  • D. H. Hardwick
  • J. A. Bergdahl
  • Y. H. Ehrlich
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 221)

Summary

PAF-acether, a naturally occurring phospholipid, is a potent activator of various biological processes, including platelet aggregation. The mechanisms of action of PAF are largely unknown. We have found that the psychotropic triazolobenzodiazepine drugs, alprazolam and triazolam, potently (IC50 < lμM) inhibit PAF-induced shape change, aggregation and secretion of human platelets. These effects are specific for PAF-activation, since the responses of human platelets to other agonists (ADP, thrombin, epinephrine, collagen, arachidonate and the Ca++ ionophore, A23187) are not inhibited by these triazolobenzodiazepines. The action of triazolobenzodiazepines on PAF-induced platelet function has clinical relevance, especially in diseases where enhanced platelet aggregability may lead to thrombosis and atherosclerosis. In addition, the ability of triazolobenzodiazepines to inhibit other PAF-mediated cellular-responses, such as anaphylactic shock or bronchoconstriction, suggests that these drugs may be useful in preventing several known pathophysiological effects of PAF.

The specific antagonism of PAF action by psychotropic drugs also suggests that PAF or PAF-like phospholipids may play a role in neuronal function. This possibility was tested by examining the effects of PAF on neural cells of the clonal line NG108-15, grown in culture in a chemically defined, serum-free medium. Low concentrations of PAF (0.5–2.5μM) induced neurite extension in NG108-15 cells, whereas higher concentrations (>3μM) were cytotoxic. Using NG108-15 cells preloaded with aequorin, it was found that PAF causes an increase in intracellular ionized calcium concentration, which is dependent on the presence of extracellular calcium. These results suggest that PAF-induced Ca++ uptake may play a role in neuronal development, and that circulating PAF may contribute to the neuronal degeneration caused by the exposure of neural tissues to blood in situations such as spinal cord injury, trauma, or stroke.

Keywords

Platelet Activate Factor Human Platelet Triazole Ring Glyceryl Ether Zellweger Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • E. Kornecki
    • 1
  • R. H. Lenox
    • 1
  • D. H. Hardwick
    • 1
  • J. A. Bergdahl
    • 1
  • Y. H. Ehrlich
    • 1
  1. 1.The Neuroscience Research Unit, Department of PsychiatryUniversity of Vermont College of MedicineBurlingtonUSA

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