ROLE OF THE MICROTUBULAR SYSTEM IN PLATELET-AGGREGATION

1. Four structural systems are involved in the process of platelet act ivation that leads to aggregation: 1) the membrane system, i.e., the c ytoplasmic membrane, the dense tubular structure and the open canalicu lar structure; 2) alpha and dense granules; 3) the peripheral microtub ular coils; 4) the microfibrillar meshwork of actin-myosin bundles. 2. We added four compounds which modify cell ultrastructure to normal pl atelet-rich plasma to analyze the behavior of the structural systems o f platelet activation: vinblastine (100 mug/ml) and cimetidine (100 mu g/ml) that act on the membrane system, ticlopidine (200 mug/ml) and co lchicine (100 mug/ml) that affect primarily the microtubular structure , cytochalasin B (30 mug/ml) and phorbol myristate acetate (100 ng/ml) that act upon the granular system, and cytochalasin D (30 mug/ml) and concanavalin A (50 mug/ml) that influence the microfibrillar structur e. Platelet aggregation was stimulated by epinephrine or thrombin. 3. Cimetidine and ticlopidine prevented aggregation. However, neither sub stance affected the microtubular structure. Colchicine and cytochalasi n B only partially impaired aggregation, because pieces of microtubule s remained in the presence of these substances. The other substances d id not present anti-aggregant activity and did not preserve the microt ubules. 4. We infer that the disappearance of the microtubules is nece ssary to produce aggregation. When they remain intact no aggregation i s produced, even though the other structural systems are activated.