Platelets and Microtubules: EFFECT OF COLCHICINE AND D₂O ON PLATELET AGGREGATION AND RELEASE INDUCED BY CALCIUM IONOPHORE A23187

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Abstract

We examined the role of microtubules in platelet aggregation and secretion (release reaction) induced by the calcium ionophore A23187 (0.8-5 μM). At these concentrations, platelet aggregation was preceded by a lag period of ∼1 min. Colchicine (an agent that disrupts microtubule assembly-disassembly) was shown to bind to platelet microtubules by employing [3H]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 [14C]serotonin). Platelets were next incubated with 20-60% D2O, an agent that stabilizes microtubules. D2O overcame colchicine-induced inhibition of the lag period, aggregation, and release. D2O 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.

Authors

D. Menche, A. Israel, S. Karpatkin