Abstract
1 We have compared the effects of diflunisal on prostaglandin (PG) synthetase from human platelets and sheep seminal vesicles (SSV) by measuring malonaldehyde, PG products, and rabbit aorta contraction.
2 Aspirin inhibits PG synthetase by covalently acetylating the enzyme. Inhibition is dependent on time and aspirin concentration. Aspirin is 37-fold more potent in inhibiting enzyme in human platelets compared with enzyme from SSV.
3 Diflunisal inhibits PG synthetase from intact human platelets and SSV equally (50% inhibition at 3-5 μM). The drug does not covalently modify the enzyme, and inhibition is not time dependent. Diflunisal probably acts at a site similar to aspirin since the drug will inhibit acetylation of the enzyme by aspirin.
4 The results suggest that diflunisal is relatively less inhibitory to platelet function than is aspirin.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Majerus P. W. Editorial: Why aspirin? Circulation. 1976 Sep;54(3):357–359. doi: 10.1161/01.cir.54.3.357. [DOI] [PubMed] [Google Scholar]
- Needleman P., Minkes M., Raz A. Thromboxanes: selective biosynthesis and distinct biological properties. Science. 1976 Jul 9;193(4248):163–165. doi: 10.1126/science.945611. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- Tollefsen D. M., Feagler J. R., Majerus P. W. The binding of thrombin to the surface of human platelets. J Biol Chem. 1974 Apr 25;249(8):2646–2651. [PubMed] [Google Scholar]
- Wallach D. P., Daniels E. G. Properties of a novel preparation of prostaglandin synthetase from sheep seminal vesicles. Biochim Biophys Acta. 1971 May 4;231(3):445–457. doi: 10.1016/0005-2760(71)90112-3. [DOI] [PubMed] [Google Scholar]