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Author Stenson, W.F.; Lobos, E. url  openurl
  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 (up) 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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