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Related Experiment Videos

Xanthines inhibit human platelet aggregation induced by platelet-activating factor.

N L Misso1, P J Thompson

  • 1Department of Medicine, University of Western Australia, Queen Elizabeth II Medical Centre, Nedlands.

Clinical and Experimental Pharmacology & Physiology
|August 1, 1992
PubMed
Summary

Theophylline and enprofylline inhibit platelet activation by platelet-activating factor (PAF). However, therapeutic doses of these asthma drugs are unlikely to impact PAF-induced platelet aggregation or adenosine triphosphate (ATP) release.

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Area of Science:

  • Pharmacology
  • Immunology
  • Biochemistry

Background:

  • Platelet-activating factor (PAF) is implicated in asthma pathogenesis.
  • Anti-asthma drugs, theophylline and enprofylline, are xanthine derivatives.
  • Investigating the effects of these drugs on platelet function is crucial.

Purpose of the Study:

  • To evaluate the inhibitory effects of theophylline and enprofylline on human platelet aggregation and adenosine triphosphate (ATP) release.
  • To compare the potency of these drugs against PAF- and adenosine diphosphate (ADP)-induced platelet activation.
  • To determine if therapeutic concentrations of xanthines can inhibit PAF-induced platelet effects.

Main Methods:

  • Human platelet-rich plasma was used to assess aggregation and ATP release.

Related Experiment Videos

  • Platelet activation was induced by PAF and ADP.
  • The inhibitory concentrations (IC50) of theophylline and enprofylline were determined.

    • Main Results:

    • Enprofylline demonstrated significantly higher potency than theophylline in inhibiting PAF-induced platelet aggregation (IC50: 94.8 ± 13.2 µmol/L vs. 934.1 ± 40.1 µmol/L).
    • Xanthines were twice as effective in inhibiting PAF-induced aggregation compared to ADP-induced aggregation.
    • ATP release was 1.4 times more sensitive to xanthine inhibition than platelet aggregation.

    Conclusions:

    • High concentrations of theophylline and enprofylline inhibit PAF-induced platelet aggregation and ATP release.
    • Therapeutic concentrations of these anti-asthma drugs are unlikely to exert significant inhibitory effects on PAF-induced platelet activation.
    • The role of PAF in asthma may not be significantly modulated by therapeutic levels of theophylline and enprofylline.