Abstract
Using a radiometric technique, prostaglandin synthetase activity was measured in vitro in the microsomal fraction of 19 synovial tissues taken from 17 rheumatoid arthritis patients. The enzyme was inhibited in vitro by low concentrations of several 'aspirin-like' drugs, though paracetamol and salicylic acid were virtually inactive. While the synthetase preparations from patients receiving indomethacin, ibuprofen, or naproxen therapy exhibited considerable activity in vitro, we were unable to show any activity in preparations from patients taking aspirin, even in low doses. These findings suggest that in vivo aspirin may be unique in being an irreversible inhibitor of the enzyme, compared with other 'aspirin-like' drugs.
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- Crook D., Collins A. ,. Prostaglandin synthetase activity from human rheumatoid synovial tissue and its inhibition by non-steroidal anti-inflammatory drugs. Prostaglandins. 1975 Jun;9(6):857–865. doi: 10.1016/0090-6980(75)90074-x. [DOI] [PubMed] [Google Scholar]
- Flower R. J. Drugs which inhibit prostaglandin biosynthesis. Pharmacol Rev. 1974 Mar;26(1):33–67. [PubMed] [Google Scholar]
- Gilmore N., Vane J. R., Wyllie J. H. Prostaglandins released by the spleen. Nature. 1968 Jun 22;218(5147):1135–1140. doi: 10.1038/2181135a0. [DOI] [PubMed] [Google Scholar]
- Kaley G., Weiner R. Prostaglandin E-1: a potential mediator of the inflammatory response. Ann N Y Acad Sci. 1971 Apr 30;180:338–350. doi: 10.1111/j.1749-6632.1971.tb53203.x. [DOI] [PubMed] [Google Scholar]
- 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]
- Levine L. Antibodies to pharmacologically active molecules: specificities and some applications of antiprostaglandins. Pharmacol Rev. 1973 Jun;25(2):293–307. [PubMed] [Google Scholar]
- Piper P., Vane J. The release of prostaglandins from lung and other tissues. Ann N Y Acad Sci. 1971 Apr 30;180:363–385. doi: 10.1111/j.1749-6632.1971.tb53205.x. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Smith M. J., Ford-Hutchinson A. W., Elliott P. N. Prostaglandins and the anti-inflammatory activities of aspirin and sodium salicylate. J Pharm Pharmacol. 1975 Jul;27(7):473–478. doi: 10.1111/j.2042-7158.1975.tb09487.x. [DOI] [PubMed] [Google Scholar]
- Smith W. L., Lands W. E. Stimulation and blockade of prostaglandin biosynthesis. J Biol Chem. 1971 Nov;246(21):6700–6702. [PubMed] [Google Scholar]
- 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]
- Willis A. L. Parallel assay of prostaglandin-like activity in rat inflammatory exudate by means of cascade superfusion. J Pharm Pharmacol. 1969 Feb;21(2):126–128. doi: 10.1111/j.2042-7158.1969.tb08213.x. [DOI] [PubMed] [Google Scholar]