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Author (up) Stenson, W.F.; Lobos, E.
Title Inhibition of platelet thromboxane synthetase by sulfasalazine Type Journal Article
Year 1983 Publication Biochemical Pharmacology Abbreviated Journal Biochem Pharmacol
Volume 32 Issue 14 Pages 2205-2209
Keywords Aminosalicylic Acids/pharmacology; Arachidonate Lipoxygenases; Arachidonic Acids/metabolism; Blood Platelets/*enzymology; Cyclooxygenase Inhibitors; Humans; In Vitro Techniques; Intestinal Mucosa/metabolism; Lipoxygenase Inhibitors; Mesalamine; Neutrophils/enzymology; Oxidoreductases/*antagonists & inhibitors; Sulfasalazine/*pharmacology; Thromboxane B2/metabolism; Thromboxane-A Synthase/*antagonists & inhibitors
Abstract Sulfasalazine is a potent antiinflammatory drug used in the treatment of ulcerative colitis. The mechanism of action of sulfasalazine is unknown but a recent study [W. F. Stenson and E. Lobos, J. clin. Invest. 69, 494 (1982)] demonstrated that sulfasalazine, at therapeutic concentrations, blocks human neutrophil lipoxygenase, suggesting that its antiinflammatory effects may be mediated in part by the inhibition of the synthesis of the chemotactic lipids 5-hydroxy-6,8,11, 14-eicosatetraenoic acid (5-HETE) and leukotriene B4 (LTB4). In the present study the effect of sulfasalazine on metabolism of exogenous arachidonic acid by human platelets was investigated. Sulfasalazine inhibited platelet thromboxane synthetase (IC50 = 0.9 mM) and partially inhibited cyclooxygenase. A methylated analog of sulfasalazine also inhibited thromboxane synthetase (IC50 = 0.3 mM) and partially inhibited cyclo-oxygenase. Neither of the cleavage products of sulfasalazine (5-aminosalicylate and sulfapyridine) inhibited thromboxane synthetase although 5-aminosalicylate blocked cyclooxygenase (IC50 = 5 mM). Neither sulfasalazine nor the methylated analog nor the cleavage products inhibited platelet lipoxygenase. This is in contrast to the inhibitory effects of sulfasalazine on neutrophil 5-lipoxygenase. The concentration of sulfasalazine in the colons of treated patients is several-fold greater than the IC50 for thromboxane synthetase.
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Language English Summary Language Original Title
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ISSN 0006-2952 ISBN Medium
Area Expedition Conference
Notes PMID:6135423 Approved no
Call Number ref @ user @ Serial 96512
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