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 verapam il (0.1, 0.2 or 0.3 mM) on platelet aggregation, on cytoplasmic Ca++ l evels and on TxB(2) production after activation of platelets with aden osine diphosphate (ADP) (100 mu M), collagen (20 mu g/ml) or thrombin (1 U/ml), A Platelet Ionized Calcium Aggregometer was used and washed, aequorin loaded platelets mere 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 concentr ations 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 las t agonists inhibition of Ca++ movements was less pronounced than inhib ition of aggregation or TxB(2) production. These data suggest that pla telet activation by collagen depends directly and almost exclusively o n Ca++ fluxes through biological membranes, while activation by ADP or thrombin is less strictly related to Ca++ movements, Indeed, with the se last two agonists verapamil may inhibit platelet activation also by calcium-independent mechanism(s).