Skip to main content
Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 1977 Oct;36(5):459–463. doi: 10.1136/ard.36.5.459

Comparison of effects of aspirin and indomethacin on human platelet prostaglandin synthetase.

D Crook, A J Collins
PMCID: PMC1000139  PMID: 411427

Abstract

Human platelets were incubated in vitro with either aspirin or indomethacin and the prostaglandin synthetase activity of the resultant microsomal fraction from each incubation measured using a radiometric technique. Whereas aspirin produced a dose-related inhibition of the enzyme, indomethacin produced little or no inhibition over the same concentration range (10(-6) mol/l--10(-3) mol/l). Furthermore, administration of aspirin (600 mg) to volunteers produced a highly significant, prolonged inhibition of platelet microsomal prostaglandin synthetase whereas no inhibition was found with indomethacin (50 mg). As indomethacin is considerably more potent than aspirin as an inhibitor of human platelet prostaglandin synthetase in vitro, the results suggest a fundamental difference in the nature of the inhibition produced by each drug, aspirin being an essentially irreversible inhibitor whereas the inhibition produced by indomethacin is reversible. Studies with [3H-acetyl] aspirin have confirmed previous findings (Roth and Majerus, 1975) that aspirin produces an irreversible acetylation of a particulate fraction protein from human platelets.

Full text

PDF
459

Selected References

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

  1. Crook D., Collins A. J., Bacon P. A., Chan R. Prostaglandin synthetase activity from human rheumatoid synovial microsomes. Effect of 'aspirin-like' drug therapy. Ann Rheum Dis. 1976 Aug;35(4):327–332. doi: 10.1136/ard.35.4.327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Flower R. J. Drugs which inhibit prostaglandin biosynthesis. Pharmacol Rev. 1974 Mar;26(1):33–67. [PubMed] [Google Scholar]
  3. Glatt M., Peskar B., Brune K. Leukocytes and prostaglandins in acute inflammation. Experientia. 1974 Nov 15;30(11):1257–1259. doi: 10.1007/BF01945171. [DOI] [PubMed] [Google Scholar]
  4. Hamberg M., Svensson J., Samuelsson B. Thromboxanes: a new group of biologically active compounds derived from prostaglandin endoperoxides. Proc Natl Acad Sci U S A. 1975 Aug;72(8):2994–2998. doi: 10.1073/pnas.72.8.2994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Kocsis J. J., Hernandovich J., Silver M. J., Smith J. B., Ingerman C. Duration of inhibition of platelet prostaglandin formation and aggregation by ingested aspirin or indomethacin. Prostaglandins. 1973 Feb;3(2):141–144. doi: 10.1016/0090-6980(73)90081-6. [DOI] [PubMed] [Google Scholar]
  6. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  7. Raz A., Stern H., Kenig-Wakshal R. Indomethacin and aspirin inhibition of prostaglandin E2 synthesis by sheep seminal vesicles microsome powder. Prostaglandins. 1973 Mar;3(3):337–352. doi: 10.1016/0090-6980(73)90072-5. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. 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]
  10. Smith W. L., Lands W. E. Stimulation and blockade of prostaglandin biosynthesis. J Biol Chem. 1971 Nov;246(21):6700–6702. [PubMed] [Google Scholar]
  11. Steiner M. Platelet protein synthesis studied in a cell-free system. Experientia. 1970;26(7):786–789. doi: 10.1007/BF02232552. [DOI] [PubMed] [Google Scholar]
  12. Stone K. J., Mather S. J., Gibson P. P. Selective inhibition of prostaglandin biosynthesis by gold salts and phenylbutazone. Prostaglandins. 1975 Aug;10(2):241–251. doi: 10.1016/0090-6980(75)90043-x. [DOI] [PubMed] [Google Scholar]
  13. Tomlinson R. V., Ringold H. J. Relationship between inhibition of prostaglandin synthesis and drug efficacy: support for the current theory on mode of action of aspirin-like drugs. Biochem Biophys Res Commun. 1972 Jan 31;46(2):552–559. doi: 10.1016/s0006-291x(72)80174-8. [DOI] [PubMed] [Google Scholar]
  14. Vane J. R. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol. 1971 Jun 23;231(25):232–235. doi: 10.1038/newbio231232a0. [DOI] [PubMed] [Google Scholar]

Articles from Annals of the Rheumatic Diseases are provided here courtesy of BMJ Publishing Group

RESOURCES