The effect of calcium channel blockers on blood platelet function, especially calcium uptake

Abstract

The effects of organic and inorganic calcium antagonists on washed platelets from rat and human been studied. Platelet aggregation was assessed by turbidimetry. Endogenous serotonin release was measured on the same sample by means of electrochemically treated carbon fiber electrodes. The organic calcium antagonist, nitrendipine, and the inorganic calcium channel blockers (Co 2+, Mn 2+, Cd 2+, La 3+) drastically inhibited rat and human platelet aggregation induced by thrombin, ADP or adrenaline in teh presence of 0.32 mM Ca 2+. In our conditions, the thrombin-induced release of endogenous serotonin was found to be external Ca 2+-dependent and completely inhibited by 20 μM nitrendipine or 1 mM Cd 2+. In addition, Ba 2+ or Sr 2+ ions can be substituted for Ca 2+ to bring about platelet aggregation as well as endogenous serotonin secretion. In Ba 2+ or Sr 2+-containing media, rat platelet aggregation and/or serotonin secretion can be inhibited by either nitrendipine or Cd 2+. Finally, we have also studied the thrombin- and external Ca 2+-dependence of radiolabeled calcium uptake by rat platelets. We found that the thrombin-induced 45Ca uptake was inhibited by either 18 μM nitrendipine or 1 mM Cd 2+. These results provide strong evidence for the existence of an influx of divalent cations (Ca 2+, Sr 2+, Ba 2+) triggering platelet function. They also suggest, although they do not prove, that the translocation of these cations occurs through an agonist-operated channel as proposed by Hallam and Rink (FEBS Lett. 186 (1986) 175–179).