The Effects of Aspirin on Megakaryocyte Prostaglandin Production

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Abstract
Aspirin inhibits the enzyme cyclooxygenase in platelets by irreversibly acetylating it. Since platelets are derived from the fragmentation of megakaryocyte cytoplasm and contain similar organelles and enzymes, the inhibitory effect of aspirin on the prostaglandin synthesis of isolated rat megakaryocytes was studied. Megakaryocytes were isolated from rat bone marrow using cellular velocity sedimentation in an isokinetic Ficoll gradient. The isolated megakaryocytes were capable of significant prostaglandin E synthesis as measured by radioimmunoassay when exposed to N-ethylmaleimide (NEM). Aspirin pretreatment in vivo abolished the ability of rat megakaryocytes to synthesize prostaglandin E. Aspirin can also acetylate irreversibly the megakaryocyte cyclooxygenase enzyme and this defect may be carried over to the newly formed platelets. These results may significantly influence the dose schedules of antiplatelet drugs currently being used in clinical trials.