Inhibition of platelet prostaglandin synthetase by oral aspirin.
Aspirin inhibits platelet function by permanently acetylating the cyclooxygenase that forms prostaglandins. We determined the sensitivity of platelets to aspirin in normal subjects by measuring [3H-acetyl]aspirin-susceptible cyclooxygenase in washed platelets obtained at various times after aspirin ingestion. A single 325-mg aspirin dose inactivated 89% of platelet cyclooxygenase. The inhibition persisted for 2 days suggesting that oral aspirin also inactivated megakaryocyte cyclooxygenase. Thereafter, active enzyme returned with a time-course reflecting platelet turnover (life-span 8.2+/-2 days). Single doses of 20-650 mg aspirin resulted in 34- greater than 95% inhibition after 24 h. Daily doses of 20-325 mg aspirin for brief periods produced 61- greater than 95% inactivation when measured 24 h after cessation of the drug. Platelet cyclooxygenase is more sensitive to inactivation by aspirin than enzyme in sheep seminal vesicles.
D000107:Acetylation; D000328:Adult; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000201:enzymology*; D016861:Cyclooxygenase Inhibitors; D006801:Humans; D008297:Male; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood; D012669:Seminal Vesicles / Q000201:enzymology; D012756:Sheep
D016861:Cyclooxygenase Inhibitors; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin