Platelets and microtubules. Effect of colchicine and D2O on platelet aggregation and release induced by calcium ionophore A23187

Abstract

We examined the role of microtubules in platelet aggregation and secretion (release reaction) induced by the calcium ionophore A23187 (0.8-5 muM). At these concentrations, platelet aggregation was preceded by a lag period of approximately 1 min. Colchicine (an agent that disrupts microtubule assembly-disassembly) was shown to bind to platelet microtubules by employing [(3)H]colchicine at a concentration that is specific for microtubules in other tissues (10 nM). Colchicine prolonged the lag period, inhibited the secondary wave of platelet aggregation, and inhibited the release reaction (release of [(14)C]serotonin). Platelets were next incubated with 20-60% D(2)O, an agent that stabilizes microtubules. D(2)O overcame colchicine-induced inhibition of the lag period, aggregation, and release. D(2)O alone enhanced platelet aggregation by 59+/-14% (SEM) and shortened the lag period by 43+/-10%. We conclude that functioning microtubules are required for platelet aggregation and release, and that microtubules of platelet preparations are functioning submaximally.