Ultrastructural features on the platelet response to phorbol myristate acetate

Phorbol myristate acetate (PMA) the active ingredient of croton oil, is a potent stimulus of irreversible platelet aggregation. The present study has examined the effects of PMA on platelet fine structure during aggregation and after incubation. PMA appears to act primarily on channels of the open canalicular system and intracellular granules. Small amounts of the agent cause dilatation of some open channels and conversion of granules to swollen vacuoles. Platelet discoid shape is not affected significantly by the changes in channels and vacuoles, and aggregation occurs without shape change. EDTA inhibits PMA-induced aggregation but does not prevent the conversion of platelet granules to vacuoles. In unstirred systems PMA causes similar changes in platelet fine structure and spontaneous aggregation. The drug appears to affect the permeability barrier separating granule contents from open channels, thereby leading to osmotic swelling of the storage organelles. PMA is the first agent observed to have a selective influence on the stability of platelet granules.