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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.
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0006-2952 ISBN Medium
Area Expedition Conference
Notes PMID:6135423 Approved no
Call Number ref @ user @ Serial 96512
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