Cytochemical electron microscopic studies of the action of phorbol myristate acetate on platelets

Phorbol myristate acetate (PMA), the active principle of croton oil, is a potent platelet aggregating agent. A previous electron microscopic study indicated that PMA caused selective labilization of platelet granules. The present investigation has employed cytochemical procedures to clarify problems concerning the action of PMA on platelets. Results of this study confirm the suggestion that vacuoles in PMA-treated platelets derive primarily from granules, and demonstrate that the swollen vacuoles are continuous with channels of the open canalicular system (OCS) and surrounding plasma. Despite loss of the barrier separating vacuolated granules from the OCS, the contents of the organelles were not extruded from the PMA aggregated platelets. Stabilization of platelet surface membranes did not inhibit the action of PMA on platelet granules, and examination of replicas of freeze-fractured PMA platelets failed to reveal any specific injury produced by the agent. The findings have elucidated some of the effects of PMA on platelet structure, but have not solved the basic mechanism of drug action.