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Decrease of platelet intracellular pH and adhesion by ticlopidine in patients with vascular disease

C Lechi1, S Gaino, G Andrioli

  • 1Institute of Medical Clinics and Chemistry and Clinic Microscopics, University of Verona, Italy.

International Angiology : a Journal of the International Union of Angiology
|July 10, 1998
PubMed
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Ticlopidine reduces platelet adhesion to fibrinogen but not collagen. This effect is not linked to changes in intracellular calcium, suggesting ticlopidine may inhibit the Na+/H+ antiport.

Area of Science:

  • Cardiovascular Research
  • Hematology
  • Pharmacology

Background:

  • Ticlopidine is an antiplatelet medication that inhibits fibrinogen binding to its receptor.
  • The study investigates ticlopidine's impact on platelet signal transduction pathways, specifically the Na+/H+ pump and intracellular calcium levels.

Purpose of the Study:

  • To determine if ticlopidine's inhibition of platelet aggregation is mediated by alterations in platelet intracellular calcium or Na+/H+ pump activity.
  • To assess the effect of ticlopidine on platelet adhesion to various surfaces and its influence on intracellular pH and calcium dynamics.

Main Methods:

  • Platelet adhesion, intracellular calcium, and intracellular pH were measured in 13 peripheral vascular disease patients before and after 30 days of ticlopidine treatment (250 mg b.i.d).

Related Experiment Videos

  • Platelet adhesion was assessed using microplates coated with plasma, fibrinogen, or collagen, with and without ADP stimulation.
  • Intracellular calcium and pH changes were measured using fluorescent indicators Fura 2 and BCECF, respectively, following stimulation with ADP and thrombin.

    • Main Results:

    • Ticlopidine significantly reduced platelet adhesion to plasma and fibrinogen by approximately 50% but did not affect adhesion to collagen.
    • No significant differences were observed in basal or ADP-induced intracellular calcium levels before and after ticlopidine treatment.
    • A significant reduction in basal intracellular pH was noted, along with a decrease in early acidification not dependent on Na+/H+ exchange.

    Conclusions:

    • The findings do not support the hypothesis that ticlopidine reduces platelet adhesion by altering intracellular calcium signaling pathways.
    • The observed reduction in basal intracellular pH and early acidification suggests a potential inhibitory effect of ticlopidine on the Na+/H+ antiport mechanism.