In vitro Effect of Verapamil on Platelet Activation Induced by ADP, Collagen or Thrombin.
We studied the effects in Vitro of the calcium channel blocker verapamil (0.1, 0.2 or 0.3 mM) on platelet aggregation, on cytoplasmic Ca(+ +) levels and on TxB(2) production after activation of platelets with adenosine diphosphate (ADP) (100 µM), collagen (20 µg/ml) or thrombin (1 U/ml). A Platelet Ionized Calcium Aggregometer was used and washed, aequorin loaded platelets were employed. The drug was able to inhibit similarly and always significantly aggregation, Ca(+ +) fluxes and TxB(2) production when collagen was the agonist. Furthermore, inhibition of aggregation and TxB(2) production was significant at all the concentrations tested when platelets were activated by ADP or thrombin, but in this case inhibition of Ca (+ +) fluxes was observed only with the higher concentrations of the drug (0.2 or 0.3 mM). Hence, with these two last agonists inhibition of Ca(+ +) movements was less pronounced than inhibition of aggregation or TxB(2) production. These data suggest that platelet activation by collagen depends directly and almost exclusively on Ca(+ +) fluxes through biological membranes, while activation by ADP or thrombin is less strictly related to Ca(+ +) movements. Indeed, with these last two agonists verapamil may inhibit platelet activation also by calcium-independent mechanism(s).
Department of Internal Medicine, Section of Medical Pathology, University of Pavia, IRCCS Policlinico S. Matteo, Pavia, Italy.
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Brocchieri
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Pacchiarini
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Saporiti
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Grignani