| Summary: | The proposal of Vane (1971) that aspirin-like drugs exert their pharmacological actions via inhibition of prostaglandin (PG) biosynthesis is now widely accepted. It was the object of the present work to prepare PG synthetase from human rheumatoid synovial tissue in order to study its basic biochemical properties, and to study the interaction(s) between the enzyme and some of the aspirin-like drugs commonly used in the therapy of the rheumatic diseases. Using a radiometric technique PG synthetase activity was measured in vitro in the microsomal fraction of 31 synovial tissues taken from 27 patients with rheumatoid arthritis. Its biochemical properties and inhibition in vitro by low concentrations of aspirin-like drugs suggested that it did not differ radically from the well-studied enzymes prepared from animal tissues. While the enzyme preparation from patients receiving indo-methacin, naproxen or ibuprofen therapy possessed considerable activity in vitro, preparations from patients receiving aspirin, even in low doses, were incapable of PG synthesis. Aspirin may therefore be unique in being an irreversible inhibitor of the enzyme. A correlation was found to exist between the potency of the aspirin-like drugs as inhibitors of synovial PG synthetase in vitro and their known therapeutic potencies. The significance of interesting anomalies such as salicylic acid is discussed. Studies of the effects of copper and copper aspirin showed interesting quantitative and qualitative effects in vitro which may have therapeutic potential. Studies with human peripheral leucocytes showed that platelets contain a high level of synthetase activity and a comparison of the effects of aspirin and indomethacin, both in vitro and in vivo confirmed the results obtained with synovial preparations. The use of [acetyl-3H] aspirin of high specific activity showed the drug to be capable of acetylating a particulate fraction protein from both platelet and synovial preparations. The possibility that this protein is the cyclo-oxygenase component of the enzyme complex is discussed.
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