Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1978 Oct;75(10):5181–5184. doi: 10.1073/pnas.75.10.5181

Sensitivity of fatty acid cyclooxygenase from human aorta to acetylation by aspirin.

J W Burch, N L Baenziger, N Stanford, P W Majerus
PMCID: PMC336289  PMID: 105363

Abstract

The rate of acetylation of fatty acid cyclooxygenase (prostaglandin synthase, EC 1.14.99.1) by [acetyl-3H]-aspirin was measured in microsomes from human aortas and coronary arteries and intact and disrupted human platelets. We also measured the inhibition by aspirin of prostacyclin generation from exogenous arachidonic acid in shredded human aorta. Cyclooxygenase in human aorta and coronary artery microsomes is approximately 1/250th as sensitive to aspirin as enzyme in intact platelets, and 1/60th as sensitive to aspirin as enzyme measured in a platelet microsomal preparation. On the basis of the in vitro data presented, we predict that small oral doses of aspirin are sufficient to inhibit platelet prostaglandin production but are not sufficient to substantially affect aorta or coronary artery prostaglandin production.

Full text

PDF
5181

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baenziger N. L., Dillender M. J., Majerus P. W. Cultured human skin fibroblasts and arterial cells produce a labile platelet-inhibitory prostaglandin. Biochem Biophys Res Commun. 1977 Sep 9;78(1):294–301. doi: 10.1016/0006-291x(77)91253-0. [DOI] [PubMed] [Google Scholar]
  2. Burch J. W., Stanford N., Majerus P. W. Inhibition of platelet prostaglandin synthetase by oral aspirin. J Clin Invest. 1978 Feb;61(2):314–319. doi: 10.1172/JCI108941. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Elwood P. C., Cochrane A. L., Burr M. L., Sweetnam P. M., Williams G., Welsby E., Hughes S. J., Renton R. A randomized controlled trial of acetyl salicylic acid in the secondary prevention of mortality from myocardial infarction. Br Med J. 1974 Mar 9;1(5905):436–440. doi: 10.1136/bmj.1.5905.436. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ferreira S. H., Moncada S., Vane J. R. Indomethacin and aspirin abolish prostaglandin release from the spleen. Nat New Biol. 1971 Jun 23;231(25):237–239. doi: 10.1038/newbio231237a0. [DOI] [PubMed] [Google Scholar]
  5. Majerus P. W., Stanford N. Comparative effects of aspirin and diflunisal on prostaglandin synthetase from human platelets and sheep seminal vesicles. Br J Clin Pharmacol. 1977 Feb;4 (Suppl 1):15S–18S. doi: 10.1111/j.1365-2125.1977.tb04509.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Marcus A. J. Aspirin and thromboembolism--a possible dilemma. N Engl J Med. 1977 Dec 8;297(23):1284–1285. doi: 10.1056/NEJM197712082972312. [DOI] [PubMed] [Google Scholar]
  7. Mielke C. H., Jr, Kaneshiro M. M., Maher I. A., Weiner J. M., Rapaport S. I. The standardized normal Ivy bleeding time and its prolongation by aspirin. Blood. 1969 Aug;34(2):204–215. [PubMed] [Google Scholar]
  8. Moncada S., Higgs E. A., Vane J. R. Human arterial and venous tissues generate prostacyclin (prostaglandin x), a potent inhibitor of platelet aggregation. Lancet. 1977 Jan 1;1(8001):18–20. doi: 10.1016/s0140-6736(77)91655-5. [DOI] [PubMed] [Google Scholar]
  9. O'Brien J. R. Effects of salicylates on human platelets. Lancet. 1968 Apr 13;1(7546):779–783. doi: 10.1016/s0140-6736(68)92228-9. [DOI] [PubMed] [Google Scholar]
  10. Roth G. J., Majerus P. W. The mechanism of the effect of aspirin on human platelets. I. Acetylation of a particulate fraction protein. J Clin Invest. 1975 Sep;56(3):624–632. doi: 10.1172/JCI108132. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Roth G. J., Stanford N., Majerus P. W. Acetylation of prostaglandin synthase by aspirin. Proc Natl Acad Sci U S A. 1975 Aug;72(8):3073–3076. doi: 10.1073/pnas.72.8.3073. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Smith J. B., Willis A. L. Aspirin selectively inhibits prostaglandin production in human platelets. Nat New Biol. 1971 Jun 23;231(25):235–237. doi: 10.1038/newbio231235a0. [DOI] [PubMed] [Google Scholar]
  13. Stanford N., Roth G. J., Shen T. Y., Majerus P. W. Lack of covalent modification of prostaglandin synthetase (cyclo-oxygenase) by indomethacin. Prostaglandins. 1977 Apr;13(4):669–675. doi: 10.1016/0090-6980(77)90237-4. [DOI] [PubMed] [Google Scholar]
  14. Whittaker N., Bunting S., Salmon J., Moncada S., Vane J. R., Johnson R. A., Morton D. R., Kinner J. H., Gorman R. R., McGuire J. C. The chemical structure of prostaglandin X (prostacyclin). Prostaglandins. 1976 Dec;12(6):915–928. doi: 10.1016/0090-6980(76)90126-x. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES