Recovery of cyclooxygenase activity after aspirin in populations of platelets separated on stractan density gradients.
Human platelets obtained before and at intervals up to one week following the ingestion of 650 mg acetylsalicylic acid (ASA) were subjected to fractionation on discontinuous gradients of stractan. Platelets were recovered from the density gradients and incubated with arachidonate. Thromboxane synthesis was estimated by radioimmunoassay (RIA). There were no differences in cyclooxygenase activity among the platelet fractions prior to ASA ingestion. ASA inhibited synthesis of thromboxane B2 (TXB2) by 98% in all subfractions. Twenty-four hours after ASA ingestion the total platelet population exhibited 10% of the control cyclooxygenase activity suggesting that new platelets emerging from the bone marrow within 24 hours of an ASA dose have functional cyclooxygenase enzymes. The pattern of return of TXB2 synthesis differed markedly among the platelet fractions, indicating differences in the distribution of new platelets among these fractions. New platelets with functional cyclooxygenase enzyme were twice as concentrated in the less dense fractions as in the most dense fraction. By 72 hours up to 75% of the platelets in the less dense fractions synthesized thromboxanes, while only 27% of platelets in the most dense fraction were active. Newly formed platelets may increase in density as they age or platelets of low density have a more rapid turnover than platelets of high density.
D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects*; D002469:Cell Separation; D002470:Cell Survival; D002499:Centrifugation, Density Gradient; D006801:Humans; D066298:In Vitro Techniques; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood*; D013929:Thromboxane B2 / Q000097:blood; D013997:Time Factors
D013929:Thromboxane B2; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin