EFFECTS OF A MICROTUBULE STABILIZING AGENT ON THE RESPONSE OF PLATELETS TO VINCRISTINE

  • 1 January 1982
    • journal article
    • research article
    • Vol. 60  (2) , 474-483
Abstract
The discoid shape of [human] blood platelets is supported by a circumferential bundle of microtubules. Removal of the microtubules by an antimitotic drug, vincristine, was associated with loss of lentiform appearance, formation of tubulin paracrystals, a depressed response to aggregating agents, and impaired secretory activity. The action of vincristine on platelet secretion and aggregation may be directly related to its action on microtubules, while other work has indicated that the antimitotic drug prevented the release reaction by inhibiting prostaglandin synthesis. The influence of taxol, a microtubule stabilizing agent, on the response of platelets to vincristine was examined. Taxol completely prevented vincristine-induced shape change, microtubule disassembly and tubulin paracrystal formation, even at concentrations 1/10 that of the antimitotic drug. Pretreatment with vincristine to dissociate microtubules and convert tubulin to crystals before exposure to taxol did not affect altered shape or tubulin paracrystals but did cause assembly of free pools of tubulin into tubular polymers. Vincristine, in amounts that remove microtubules, depressed platelet aggregation and secretion, effects that could be overcome by increasing agonist concentration. Although completely preventing microtubule dissociation, taxol had no corrective influence on vincristine-induced inhibition of platelet function. Vincristine concentrations that disassembled microtubules and blocked secretion did not ihibit conversion of 14C-arachidonic acid to thromboxane B2. Vincristine apparently inhibits platelet function through some mechanism other than disassembling microtubules, but the other mechanism does not involve inhibition of prostaglandin synthesis.