Unsere Experimente belegen, dass SASP in therapeutisch erreichbaren Konzentrationen sowohl die Leukotrien- als auch die Thromboxansynthese vollständig blockieren kann. Im Gegensatz zu SASP hemmt die 5-ASA nur die TxA2-Synthese für eine ausreichende therapeutische Wirkung. Klinische Studien mit selektiven Inhibitoren haben jedoch gezeigt, dass weder die selektive Hemmung der Leukotriensynthese noch die selektive Hemmung der Thromboxansynthese für eine therapeutische Wirkung bei den entzündlichen Darmerkrankungen ausreichend ist.
Eine Vielzahl von Publikationen belegen, dass 5-ASA ein wesentlich potenterer Sauerstoffradikalfänger ist als SASP. Beide Substanzen beeinflussen somit ganz unterschiedliche Entzündungsmediatorsystem. Da sowohl bei den entzündlichen Darmerkrankungen als auch bei der chronischen Polyarthritis das Immunsystem eine wichtige Rolle spielt, dürfte die Beeinflussung von NFκB für beide ein wichtiger weiterer pharmakologischer Angriffspunkt sein. Aus diesen Befunden folgt, dass es die Vielzahl der pharmakologischen Angriffspunkte ist, die zur therapeutischen Wirkung von SASP und 5-ASA bei den entzündlichen Darmerkrankungen und bei der chronischen Polyarthritis beitragen.
7 Literatur
1. Rains, C.P., Noble, S., and Faulds, D. 1995. Sulfasalazine A review of its
Pharmacological Properties and Therapeutic Efficacy in the Treatment of Rheumatoid Arthritis. Drug Evaluation 50:137-156.
2. Herrlinger, K., Fellermann, K., and Stange, E.F. 2002. Standard therapy of ulcerative colitis. Evidence- and consensus-based recommendations. Internist (Berl) 43:1367-1368, 1371-1365.
3. Hoffmann, J.C., Zeitz, M., Bischoff, S.C., Brambs, H.J., Bruch, H.P., Buhr, H.J., Dignass, A., Fischer, I., Fleig, W., Folsch, U.R., et al. 2004. Diagnosis and therapy of ulcerative colitis: results of an evidence based consensus conference by the German society of Digestive and Metabolic Diseases and the competence network on
inflammatory bowel disease. Z Gastroenterol 42:979-983.
4. Hoffmann, J.C., and Zeitz, M. 2002. [Standard therapy of Crohn disease. Consensus-based recommendations]. Internist (Berl) 43:1376, 1379-1385.
5. Stange, E.F., Schreiber, S., Folsch, U.R., von Herbay, A., Scholmerich, J., Hoffmann, J., Zeitz, M., Fleig, W.E., Buhr, H.J., Kroesen, A.J., et al. 2003. Diagnostics and treatment of Crohn's disease -- results of an evidence-based consensus conference of the German Society for Digestive and Metabolic Diseases. Z Gastroenterol 41:19-20.
6. Bachrach, W.H. 1988. Sulfasalazine: I. An historical perspective. Am J Gastroenterol 83:487-496.
7. Svartz, N. 1988. Sulfasalazine: II. Some notes on the discovery and development of salazopyrin. Am J Gastroenterol 83:497-503.
8. Egan, L.J., and Sandborn, W.J. 2004. Advances in the treatment of Crohn's disease.
Gastroenterology 126:1574-1581.
9. Hanauer, S.B. 2004. Medical therapy for ulcerative colitis 2004. Gastroenterology 126:1582-1592.
10. Misiewicz, J.J., Lennard-Jones, J.E., Connell, A.M., Baron, J.H., and Jones, F.A. 1965.
Controlled trial of sulphasalazine in maintenance in therapy for ulcerative colitis.
Lancet 1:185-188.
11. Azad Khan, A.K., Piris, J., and Truelove, S.C. 1977. An experiment to determine the active therapeutic moiety of sulphasalazine. Lancet 2:892-895.
12. Schroder, H., and Campbell, D.E. 1972. Absorption, metabolism, and excretion of salicylazosulfapyridine in man. Clin Pharmacol Ther 13:539-551.
13. Peppercorn, M.A. 1990. Advances in drug therapy for inflammatory bowel disease. Ann Intern Med 112:50-60.
14. Ransford, R.A., and Langman, M.J. 2002. Sulphasalazine and mesalazine: serious adverse reactions re-evaluated on the basis of suspected adverse reaction reports to the Committee on Safety of Medicines. Gut 51:536-539.
15. Di Paolo, M.C., Paoluzi, O.A., Pica, R., Iacopini, F., Crispino, P., Rivera, M., Spera,
18. Ward, M.M., and Fries, J.F. 1998. Trends in antirheumatic medication use among patients with rheumatoid arthritis, 1981-1996. J Rheumatol 25:408-416.
19. Ward, J.R. 1990. Challenging the pyramid. A new look at therapeutic approaches for rheumatoid arthritis. Earlier intervention with second line therapies. J Rheumatol Suppl 25:18-23.
20. Yelin, E.H., Henke, C.J., and Epstein, W.V. 1986. Work disability among persons with musculoskeletal conditions. Arthritis Rheum 29:1322-1333.
21. Yelin, E., Henke, C., and Epstein, W. 1987. The work dynamics of the person with rheumatoid arthritis. Arthritis Rheum 30:507-512.
22. Markenson, J.A. 1991. Worldwide trends in the socioeconomic impact and long-term prognosis of rheumatoid arthritis. Semin Arthritis Rheum 21:4-12.
23. Symmons, D.P. 1988. Mortality in rheumatoid arthritis. Br J Rheumatol 27 Suppl 1:44-54.
24. Isomaki, H.A. 1989. Rheumatoid arthritis as seen from official data registers.
Experience in Finland. Scand J Rheumatol Suppl 79:21-24.
25. Fries, J. 1996. Toward an understanding of NSAID-related adverse events: the contribution of longitudinal data. Scand J Rheumatol Suppl 102:3-8.
26. Fries, J.F., Williams, C.A., Ramey, D.R., and Bloch, D.A. 1993. The relative toxicity of alternative therapies for rheumatoid arthritis: implications for the therapeutic
progression. Semin Arthritis Rheum 23:68-73.
27. McConkey, B., Amos, R.S., Durham, S., Forster, P.J., Hubball, S., and Walsh, L. 1980.
Sulphasalazine in rheumatoid arthritis. Br Med J 280:442-444.
28. Felson, D.T., Anderson, J.J., and Meenan, R.F. 1990. The comparative efficacy and toxicity of second-line drugs in rheumatoid arthritis. Results of two metaanalyses.
Arthritis Rheum 33:1449-1461.
29. Felson, D.T., Anderson, J.J., and Meenan, R.F. 1992. Use of short-term
efficacy/toxicity tradeoffs to select second-line drugs in rheumatoid arthritis. A metaanalysis of published clinical trials. Arthritis Rheum 35:1117-1125.
30. Porter, D.R., and Capell, H.A. 1990. The use of sulphasalazine as a disease modifying antirheumatic drug. Baillieres Clin Rheumatol 4:535-551.
31. van der Heijde, D.M., van Riel, P.L., Nuver-Zwart, I.H., Gribnau, F.W., and vad de Putte, L.B. 1989. Effects of hydroxychloroquine and sulphasalazine on progression of joint damage in rheumatoid arthritis. Lancet 1:1036-1038.
32. Pullar, T., Hunter, J.A., and Capell, H.A. 1985. Which component of sulphasalazine is active in rheumatoid arthritis? Br Med J (Clin Res Ed) 290:1535-1538.
33. Neumann, V.C., Taggart, A.J., Le Gallez, P., Astbury, C., Hill, J., and Bird, H.A. 1986.
A study to determine the active moiety of sulphasalazine in rheumatoid arthritis. J Rheumatol 13:285-287.
34. Taggart, A.J., Neumann, V.C., Hill, J., Astbury, C., Le Gallez, P., and Dixon, J.S. 1986.
5-Aminosalicylic acid or sulphapyridine. Which is the active moiety of sulphasalazine in rheumatoid arthritis? Drugs 32 Suppl 1:27-34.
35. Bird, H. 1995. Sulphasalazine, Sulphapyridine or 5-Aminosalicylic acid - which is the active moiety in rheumatoid arthritis. British Journal of Rheumatology 34 (suppl. 2):16-19.
36. O'Dell, J.R., Leff, R., Paulsen, G., Haire, C., Mallek, J., Eckhoff, P.J., Fernandez, A., Blakely, K., Wees, S., Stoner, J., et al. 2002. Treatment of rheumatoid arthritis with methotrexate and hydroxychloroquine, methotrexate and sulfasalazine, or a
combination of the three medications: results of a two-year, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 46:1164-1170.
37. Cannella, A.C., and O'Dell, J.R. 2003. Is there still a role for traditional disease-modifying antirheumatic drugs (DMARDs) in rheumatoid arthritis? Curr Opin Rheumatol 15:185-192.
38. Joos, R., Veys, E.M., Mielants, H., van Werveke, S., and Goemaere, S. 1991.
Sulfasalazine treatment in juvenile chronic arthritis: an open study. J Rheumatol 18:880-884.
39. Das, K.M., Chowdhury, J.R., Zapp, B., and Fara, J.W. 1979. Small bowel absorption of sulfasalazine and its hepatic metabolism in human beings, cats, and rats.
Gastroenterology 77:280-284.
40. Peppercorn, M.A., and Goldman, P. 1972. The role of intestinal bacteria in the metabolism of salicylazosulfapyridine. J Pharmacol Exp Ther 181:555-562.
41. van Hogezand, R.A., van Hees, P.A., Zwanenburg, B., van Rossum, J.M., and van Tongeren, J.H. 1985. Disposition of disodium azodisalicylate in healthy subjects. A possible new drug for inflammatory bowel disease. Gastroenterology 88:717-722.
42. Allgayer, H., Ahnfelt, N.O., Kruis, W., Klotz, U., Frank-Holmberg, K., Soderberg, H.N., and Paumgartner, G. 1989. Colonic N-acetylation of 5-aminosalicylic acid in inflammatory bowel disease. Gastroenterology 97:38-41.
43. Ireland, A., Priddle, J.D., and Jewell, D.P. 1990. Acetylation of 5-aminosalicyclic acid by human colonic epithelial cells. Clincal Science 78:105-111.
44. Ryde, M., Sander, H., and Ehrnebo, M. 1993. Steady state dose proportionality study of Salazopyrin EN in healthy volunteers. Pharmacia Document 9300811.
45. Klotz, U. 1985. Clinical pharmacokinetics of sulphasalazine, its metabolites and other prodrugs of 5-aminosalicylic acid. Clin Pharmacokinet 10:285-302.
46. Ireland, A., Priddle, J.D., and Jewell, D.P. 1992. Comparison of 5-aminosalicylic acid and N-acetylaminosalicylic acid uptake by the isolated human colonic epithelial cell.
Gut 33:1343-1347.
47. Binder, V., Halskov, S., and Hvidberg, E.F. 1981. A controlled study of 5-acetaminosalicylic acid as enema in ulcerative colitis. Scandinavian Journal of Gastroenterology 16:1122.
48. van Hogezand, R.A., van Hees, P.A., van Gorp, J.P., van Lier, H.J., Bakker, J.H., Wesseling, P., van Haelst, U.J., and van Tongeren, J.H. 1988. Double-blind comparison of 5-aminosalicylic acid and acetyl-5-aminosalicylic acid suppositories in patients with idiopathic proctitis. Aliment Pharmacol Ther 2:33-40.
49. Hanngren, A., Hansson, E., Svartz, N., and Ullberg, S. 1963. Distribution and
metabolism of salicyl-azo-sulfapyridine. II. A study with S35-salicyl-azo-sulfapyridine and S35-sulfapyridine. Acta Med Scand 173:391-399.
50. Hanngren, A., Hansson, E., Svartz, N., and Ullberg, S. 1963. Distribution and
metabolism of salicyl-azo-sulfapyridine. I. A study with C-14-5-amino-salicylic acid.
Acta Med Scand 173:61-72.
51. Farr, M., Brodrick, A., and Bacon, P.A. 1985. Plasma and synovial fluid concentrations of sulphasalazine and two of its metabolites in rheumatoid arthritis. Rheumatol Int 5:247-251.
52. Bates, T.R., Blumenthal, H.P., and Pieniaszek, H.J., Jr. 1977. Salivary excretion and
54. Azadkhan, A.K., Truelove, S.C., and Aronson, J.K. 1982. The disposition and
metabolism of sulphasalazine (salicylazosulphapyridine) in man. Br J Clin Pharmacol 13:523-528.
55. Das, K.M., and Dubin, R. 1976. Clinical pharmacokinetics of sulphasalazine. Clin Pharmacokinet 1:406-425.
56. Schroder, H., and Evans, D.A. 1972. The polymorphic acetylation of sulphapyridine in man. J Med Genet 9:168-171.
57. Podolsky, D.K. 2002. Inflammatory bowel disease. N Engl J Med 347:417-429.
58. Choy, E.H., and Panayi, G.S. 2001. Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med 344:907-916.
59. Travis, S.P., and Jewell, D.P. 1994. Salicylates for ulcerative colitis--their mode of action. Pharmacol Ther 63:135-161.
60. Gaginella, T.S., and Walsh, R.E. 1992. Sulfasalazine. Multiplicity of action. Dig Dis Sci 37:801-812.
61. MacDermott, R.P., and Stenson, W.F. 1988. Alterations of the immune system in ulcerative colitis and Crohn's disease. Adv Immunol 42:285-328.
62. Comer, S.S., and Jasin, H.E. 1988. In vitro immunomodulatory effects of sulfasalazine and its metabolites. J Rheumatol 15:580-586.
63. Imai, F., Suzuki, T., Ishibashi, T., and Dohi, Y. 1991. Effect of sulfasalazine on B cells.
Clin Exp Rheumatol 9:259-264.
64. Gibson, P.R., and Jewell, D.P. 1985. Sulphasalazine and derivatives, natural killer activity and ulcerative colitis. Clin Sci (Lond) 69:177-184.
65. Aparicio-Pages, M.N., Verspaget, H.W., Hafkenscheid, J.C., Crama-Bohbouth, G.E., Pena, A.S., Weterman, I.T., and Lamers, H.W. 1990. Inhibition of cell mediated cytotoxicity by sulphasalazine: effect of in vivo treatment with 5-aminosalicylic acid and sulphasalazine on in vitro natural killer cell activity. Gut 31:1030-1032.
66. Molin, L., and Stendahl, O. 1979. The effect of sulfasalazine and its active components on human polymorphonuclear leukocyte function in relation to ulcerative colitis. Acta Med Scand 206:451-457.
67. Rhodes, J.M., Bartholomew, T.C., and Jewell, D.P. 1981. Inhibition of leucocyte motility by drugs used in ulcerative colitis. Gut 22:642-647.
68. Brynskov, J., Nielsen, O.H., Ahnfelt-Ronne, I., and Bendtzen, K. 1994. Cytokines (immunoinflammatory hormones) and their natural regulation in inflammatory bowel disease (Crohn's disease and ulcerative colitis): a review. Dig Dis 12:290-304.
69. Quinn, M.T., and Gauss, K.A. 2004. Structure and regulation of the neutrophil respiratory burst oxidase: comparison with nonphagocyte oxidases. J Leukoc Biol 76:760-781.
70. Hiller, K.O., and Wilson, R.L. 1983. Hydroxyl-free radicals and anti-inflammatory drugs: biological inactivation studies and reaction rate constants. Biochem Pharmacol 32:2109-2111.
71. Ahnfelt-Ronne, I., Nielsen, O.H., Bukhave, K., and Elmgreen, J. 1987. Sulfasalazine and its anti-inflammatory metabolite, 5-aminosalicylic acid: effect on arachidonic acid metabolism in human neutrophils, and free radical scavenging. Adv Prostaglandin Thromboxane Leukot Res 17B:918-922.
72. Ahnfelt-Ronne, I., and Nielsen, O.H. 1987. The antiinflammatory moiety of
sulfasalazine, 5-aminosalicylic acid, is a radical scavenger. Agents Actions 21:191-194.
73. Dull, B.J., Salata, K., Van Langenhove, A., and Goldman, P. 1987. 5-Aminosalicylate:
oxidation by activated leukocytes and protection of cultured cells from oxidative damage. Biochem Pharmacol 36:2467-2472.
74. Miles, A.M., and Grisham, M.B. 1995. Antioxidant properties of 5-aminosalicylic acid:
potential mechanism for its protective effect in ulcerative colitis. Adv Exp Med Biol 371B:1317-1321.
75. Williams, J.G., and Hallett, M.B. 1989. The reaction of 5-amino-salicylic acid with hypochlorite. Implications for its mode of action in inflammatory bowel disease.
Biochem Pharmacol 38:149-154.
76. Williams, J.G., and Hallett, M.B. 1989. Effect of sulphasalazine and its active metabolite, 5-amino-salicylic acid, on toxic oxygen metabolite production by neutrophils. Gut 30:1581-1587.
77. Dallegri, F., Ottonello, L., Ballestrero, A., Bogliolo, F., Ferrando, F., and Patrone, F.
1990. Cytoprotection against neutrophil derived hypochlorous acid: a potential
mechanism for the therapeutic action of 5-aminosalicylic acid in ulcerative colitis. Gut 31:184-186.
78. Kettle, A.J., and Winterbourn, C.C. 1991. Mechanism of inhibition of myeloperoxidase by anti-inflammatory drugs. Biochem Pharmacol 41:1485-1492.
79. Carlin, G., Djursater, R., Smedegard, G., and Gerdin, B. 1985. Effect of anti-inflammatory drugs on xanthine oxidase and xanthine oxidase induced depolymerization of hyaluronic acid. Agents Actions 16:377-384.
80. Keshavarzian, A., Morgan, G., Sedghi, S., Gordon, J.H., and Doria, M. 1990. Role of reactive oxygen metabolites in experimental colitis. Gut 31:786-790.
81. Schottelius, A.J., and Baldwin, A.S., Jr. 1999. A role for transcription factor NF-kappa B in intestinal inflammation. Int J Colorectal Dis 14:18-28.
82. Barnes, P.J., and Karin, M. 1997. Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. N Engl J Med 336:1066-1071.
83. Bouma, G., and Strober, W. 2003. The immunological and genetic basis of inflammatory bowel disease. Nat Rev Immunol 3:521-533.
84. Wahl, C., Liptay, S., Adler, G., and Schmid, R.M. 1998. Sulfasalazine: a potent and specific inhibitor of nuclear factor kappa B. J Clin Invest 101:1163-1174.
85. Weber, C.K., Liptay, S., Wirth, T., Adler, G., and Schmid, R.M. 2000. Suppression of NF-kappaB activity by sulfasalazine is mediated by direct inhibition of IkappaB kinases alpha and beta. Gastroenterology 119:1209-1218.
86. Cavallini, L., Francesconi, M.A., Zoccarato, F., and Alexandre, A. 2001. Involvement of nuclear factor-kappa B (NF-kappaB) activation in mitogen-induced lymphocyte proliferation: inhibitory effects of lymphoproliferation by salicylates acting as NF-kappaB inhibitors. Biochem Pharmacol 62:141-147.
87. Eliakim, R., Karmeli, F., Razin, E., and Rachmilewitz, D. 1988. Role of platelet-activating factor in ulcerative colitis. Enhanced production during active disease and inhibition by sulfasalazine and prednisolone. Gastroenterology 95:1167-1172.
88. Rachmilewitz, D., Karmeli, F., and Eliakim, R. 1990. Platelet-activating factor--a possible mediator in the pathogenesis of ulcerative colitis. Scand J Gastroenterol Suppl 172:19-21.
89. Capasso, F., Tavares, I.A., and Bennett, A. 1991. Release of platelet-activating factor (PAF) from human colon mucosa and its inhibition by 5-aminosalicylic acid. Drugs
93. Sears, D.M., Avots-Avotins, A., Culp, K., and Gavin, M.W. 2004. Frequency and clinical outcome of capsule retention during capsule endoscopy for GI bleeding of obscure origin. Gastrointest Endosc 60:822-827.
94. Davies, N.M. 1995. Toxicity of nonsteroidal anti-inflammatory drugs in the large intestine. Dis Colon Rectum 38:1311-1321.
95. Hawkey, C.J., Boughton-Smith, N.K., and Whittle, B.J. 1985. Modulation of human colonic arachidonic acid metabolism by sulfasalazine. Dig Dis Sci 30:1161-1165.
96. Krause, W., and DuBois, R.N. 2000. Eicosanoids and the large intestine.
Prostaglandins Other Lipid Mediat 61:145-161.
97. Atay, S., Tarnawski, A.S., and Dubois, A. 2000. Eicosanoids and the stomach.
Prostaglandins Other Lipid Mediat 61:105-124.
98. Lauritsen, K., Laursen, L.S., Bukhave, K., and Rask-Madsen, J. 1988. In vivo profiles of eicosanoids in ulcerative colitis, Crohn's colitis, and Clostridium difficile colitis.
Gastroenterology 95:11-17.
99. Koshihara, Y., Isono, T., Oda, H., Karube, S., and Hayashi, Y. 1988. Measurement of sulfidopeptide leukotrienes and their metabolism in human synovial fluid of patients with rheumatoid arthritis. Prostaglandins Leukot Essent Fatty Acids 32:113-119.
100. Ahmadzadeh, N., Shingu, M., Nobunaga, M., and Tawara, T. 1991. Relationship between leukotriene B4 and immunological parameters in rheumatoid synovial fluids.
Inflammation 15:497-503.
101. Fauler, J., Thon, A., Tsikas, D., von der Hardt, H., and Frolich, J.C. 1994. Enhanced synthesis of cysteinyl leukotrienes in juvenile rheumatoid arthritis. Arthritis Rheum 37:93-97.
102. Nakamura, H., Hishinuma, T., Suzuki, N., Chiba, S., Tsukamoto, H., Takabatake, M., Sawai, T., Mitomo, T., Inoue, H., Matsumoto, F., et al. 2001. Difference in urinary 11-dehydro TXB2 and LTE4 excretion in patients with rheumatoid arthritis.
Prostaglandins Leukot Essent Fatty Acids 65:301-306.
103. Lewis, R.A., Austen, K.F., and Soberman, R.J. 1990. Leukotrienes and other products of the 5-lipoxygenase pathway. Biochemistry and relation to pathobiology in human diseases. N Engl J Med 323:645-655.
104. Keppler, D. 1992. Leukotrienes: biosynthesis, transport, inactivation, and analysis. Rev Physiol Biochem Pharmacol 121:1-30.
105. Murakami, M., and Kudo, I. 2002. Phospholipase A2. J Biochem (Tokyo) 131:285-292.
106. Kudo, I., and Murakami, M. 2002. Phospholipase A2 enzymes. Prostaglandins Other Lipid Mediat 68-69:3-58.
107. Nakatani, Y., Sunaga, S., Murakami, M., and Kudo, I. 2002. Cytosolic phospholipase A2 alpha interacts with microtubules. Adv Exp Med Biol 507:21-24.
108. Radmark, O. 2002. Arachidonate 5-lipoxygenase. Prostaglandins Other Lipid Mediat 68-69:211-234.
109. Glover, S., de Carvalho, M.S., Bayburt, T., Jonas, M., Chi, E., Leslie, C.C., and Gelb, M.H. 1995. Translocation of the 85-kDa phospholipase A2 from cytosol to the nuclear envelope in rat basophilic leukemia cells stimulated with calcium ionophore or
IgE/antigen. J Biol Chem 270:15359-15367.
110. Kargman, S., Vickers, P.J., and Evans, J.F. 1992. A23187-induced translocation of 5-lipoxygenase in osteosarcoma cells. J Cell Biol 119:1701-1709.
111. Rouzer, C.A., and Kargman, S. 1988. Translocation of 5-lipoxygenase to the membrane in human leukocytes challenged with ionophore A23187. J Biol Chem 263:10980-10988.
112. Woods, J.W., Evans, J.F., Ethier, D., Scott, S., Vickers, P.J., Hearn, L., Heibein, J.A., Charleson, S., and Singer, II. 1993. 5-lipoxygenase and 5-lipoxygenase-activating protein are localized in the nuclear envelope of activated human leukocytes. J Exp Med 178:1935-1946.
113. Dixon, R.A., Diehl, R.E., Opas, E., Rands, E., Vickers, P.J., Evans, J.F., Gillard, J.W., and Miller, D.K. 1990. Requirement of a 5-lipoxygenase-activating protein for
leukotriene synthesis. Nature 343:282-284.
114. Miller, D.K., Gillard, J.W., Vickers, P.J., Sadowski, S., Leveille, C., Mancini, J.A., Charleson, P., Dixon, R.A., Ford-Hutchinson, A.W., Fortin, R., et al. 1990.
Identification and isolation of a membrane protein necessary for leukotriene production.
Nature 343:278-281.
115. Rouzer, C.A., Ford-Hutchinson, A.W., Morton, H.E., and Gillard, J.W. 1990. MK886, a potent and specific leukotriene biosynthesis inhibitor blocks and reverses the
membrane association of 5-lipoxygenase in ionophore-challenged leukocytes. J Biol Chem 265:1436-1442.
116. Bonizzi, G., Piette, J., Merville, M.P., and Bours, V. 2000. Cell type-specific role for reactive oxygen species in nuclear factor-kappaB activation by interleukin-1. Biochem Pharmacol 59:7-11.
117. Rouzer, C.A., Matsumoto, T., and Samuelsson, B. 1986. Single protein from human leukocytes possesses 5-lipoxygenase and leukotriene A4 synthase activities. Proc Natl Acad Sci U S A 83:857-861.
118. Samuelsson, B., and Funk, C.D. 1989. Enzymes involved in the biosynthesis of leukotriene B4. J Biol Chem 264:19469-19472.
119. Borgeat, P., and Samuelsson, B. 1979. Metabolism of arachidonic acid in
polymorphonuclear leukocytes. Structural analysis of novel hydroxylated compounds. J Biol Chem 254:7865-7869.
120. Yoshimoto, T., Soberman, R.J., Spur, B., and Austen, K.F. 1988. Properties of highly purified leukotriene C4 synthase of guinea pig lung. J Clin Invest 81:866-871.
121. Lam, B.K., and Austen, K.F. 2002. Leukotriene C4 synthase: a pivotal enzyme in cellular biosynthesis of the cysteinyl leukotrienes. Prostaglandins Other Lipid Mediat 68-69:511-520.
122. Murphy, R.C., and Zarini, S. 2002. Glutathione adducts of oxyeicosanoids.
Prostaglandins Other Lipid Mediat 68-69:471-482.
123. Samuelsson, B., Haeggstrom, J.Z., and Wetterholm, A. 1991. Leukotriene biosynthesis.
Ann N Y Acad Sci 629:89-99.
124. Peters-Golden, M. 1998. Cell biology of the 5-lipoxygenase pathway. Am J Respir Crit Care Med 157:S227-231; discussion S231-222, S247-228.
125. Samuelsson, B. 1983. Leukotrienes: mediators of immediate hypersensitivity reactions and inflammation. Science 220:568-575.
126. Marcus, A.J. 1986. Transcellular metabolism of eicosanoids. Prog Hemost Thromb 8:127-142.
127. Feinmark, S.J., and Cannon, P.J. 1987. Vascular smooth muscle cell leukotriene C4 synthesis: requirement for transcellular leukotriene A4 metabolism. Biochim Biophys
131. Toda, A., Yokomizo, T., Masuda, K., Nakao, A., Izumi, T., and Shimizu, T. 1999.
Cloning and characterization of rat leukotriene B(4) receptor. Biochem Biophys Res Commun 262:806-812.
132. Ford-Hutchinson, A.W., Bray, M.A., Doig, M.V., Shipley, M.E., and Smith, M.J. 1980.
Leukotriene B, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes. Nature 286:264-265.
133. Dahlen, S.E., Bjork, J., Hedqvist, P., Arfors, K.E., Hammarstrom, S., Lindgren, J.A., and Samuelsson, B. 1981. Leukotrienes promote plasma leakage and leukocyte adhesion in postcapillary venules: in vivo effects with relevance to the acute inflammatory response. Proc Natl Acad Sci U S A 78:3887-3891.
134. Shak, S., and Goldstein, I.M. 1984. Omega-oxidation is the major pathway for the catabolism of leukotriene B4 in human polymorphonuclear leukocytes. J Biol Chem 259:10181-10187.
135. Kaever, V., Martin, M., Fauler, J., Marx, K.H., and Resch, K. 1987. A novel metabolic pathway for leukotriene B4 in different cell types: primary reduction of a double bond.
Biochim Biophys Acta 922:337-344.
136. Fauler, J., Marx, K.H., Kaever, V., and Frolich, J.C. 1989. Human monocytes convert leukotriene B4 to two dihydro-leukotriene B4-metabolites. Prostaglandins Leukot Essent Fatty Acids 37:193-196.
137. Powell, W.S. 1987. Conversion of leukotriene B4 to dihydro and 19-hydroxy metabolites by rat polymorphonuclear leukocytes. Biochem Biophys Res Commun 145:991-998.
138. Powell, W.S., and Gravelle, F. 1989. Metabolism of leukotriene B4 to dihydro and dihydro-oxo products by porcine leukocytes. J Biol Chem 264:5364-5369.
139. Hammarstrom, S., Orning, L., and Bernstrom, K. 1985. Metabolism of leukotrienes.
Mol Cell Biochem 69:7-16.
140. Ishikawa, T., Kuo, M.T., Furuta, K., and Suzuki, M. 2000. The human multidrug resistance-associated protein (MRP) gene family: from biological function to drug molecular design. Clin Chem Lab Med 38:893-897.
141. Keppler, D., and Konig, J. 2000. Hepatic secretion of conjugated drugs and endogenous substances. Semin Liver Dis 20:265-272.
142. Keppler, D. 1999. Export pumps for glutathione S-conjugates. Free Radic Biol Med 27:985-991.
143. Keppler, D., Leier, I., and Jedlitschky, G. 1997. Transport of glutathione conjugates and glucuronides by the multidrug resistance proteins MRP1 and MRP2. Biol Chem
378:787-791.
144. Cole, S.P., and Deeley, R.G. 1998. Multidrug resistance mediated by the ATP-binding cassette transporter protein MRP. Bioessays 20:931-940.
145. Evans, J.F. 2002. Cysteinyl leukotriene receptors. Prostaglandins Other Lipid Mediat 68-69:587-597.
146. Dahlen, S.E., Hedqvist, P., Hammarstrom, S., and Samuelsson, B. 1980. Leukotrienes are potent constrictors of human bronchi. Nature 288:484-486.
147. Holgate, S.T., Peters-Golden, M., Panettieri, R.A., and Henderson, W.R., Jr. 2003.
Roles of cysteinyl leukotrienes in airway inflammation, smooth muscle function, and remodeling. J Allergy Clin Immunol 111:S18-34; discussion S34-16.
148. Horwitz, R.J., McGill, K.A., and Busse, W.W. 1998. The role of leukotriene modifiers in the treatment of asthma. Am J Respir Crit Care Med 157:1363-1371.
149. Stene, D.O., and Murphy, R.C. 1989. Sequential formation of leukotriene E4
metabolites by isolated rat hepatocytes. Adv Prostaglandin Thromboxane Leukot Res 19:108-111.
150. Huber, M., Muller, J., Leier, I., Jedlitschky, G., Ball, H.A., Moore, K.P., Taylor, G.W., Williams, R., and Keppler, D. 1990. Metabolism of cysteinyl leukotrienes in monkey and man. Eur J Biochem 194:309-315.
151. Sala, A., Voelkel, N., Maclouf, J., and Murphy, R.C. 1990. Leukotriene E4 elimination and metabolism in normal human subjects. J Biol Chem 265:21771-21778.
152. Chaney, M.O., Demarco, P.V., Jones, N.D., and Occolowitz, J.L. 1974. Letter: The structure of A23187, a divalent cation ionophore. J Am Chem Soc 96:1932-1933.
153. Gay, J.C., Beckman, J.K., Brash, A.R., Oates, J.A., and Lukens, J.N. 1984.
Enhancement of chemotactic factor-stimulated neutrophil oxidative metabolism by leukotriene B4. Blood 64:780-785.
154. Fletcher, M.P. 1986. Modulation of the heterogeneous membrane potential response of neutrophils to N-formyl-methionyl-leucyl-phenylalanine (FMLP) by leukotriene B4:
evidence for cell recruitment. J Immunol 136:4213-4219.
155. Fletcher, M.P., and Seligmann, B.E. 1986. PMN heterogeneity: long-term stability of fluorescent membrane potential responses to the chemoattractant N-formyl-methionyl-leucyl-phenylalanine in healthy adults and correlation with respiratory burst activity.
Blood 68:611-618.
156. Williams, J.D., Robin, J.L., Lewis, R.A., Lee, T.H., and Austen, K.F. 1986. Generation of leukotrienes by human monocytes pretreated with cytochalasin B and stimulated with formyl-methionyl-leucyl-phenylalanine. J Immunol 136:642-648.
157. Boyum, A. 1968. Isolation of mononuclear cells and granulocytes from human blood.
Isolation of monuclear cells by one centrifugation, and of granulocytes by combining centrifugation and sedimentation at 1 g. Scand J Clin Lab Invest Suppl 97:77-89.
158. Giannessi, D., De Caterina, R., Gazzetti, P., Bernini, W., Masini, S., and Zucchelli, G.C. 1982. Methodological assessment and applications of a radioimmunoassay for thromboxane (TxB2) to measurement of TxB2 release by platelets. J Nucl Med Allied Sci 26:25-33.
159. Lauritsen, K., Laursen, L.S., Bukhave, K., and Rask-Madsen, J. 1986. Effects of topical 5-aminosalicylic acid and prednisolone on prostaglandin E2 and leukotriene B4 levels determined by equilibrium in vivo dialysis of rectum in relapsing ulcerative colitis.
Gastroenterology 91:837-844.
160. Lobos, E.A., Sharon, P., and Stenson, W.F. 1987. Chemotactic activity in inflammatory bowel disease. Role of leukotriene B4. Dig Dis Sci 32:1380-1388.
161. Tornhamre, S., Edenius, C., Smedegard, G., Sjoquist, B., and Lindgren, J.A. 1989.
Effects of sulfasalazine and a sulfasalazine analogue on the formation of lipoxygenase and cyclooxygenase products. Eur J Pharmacol 169:225-234.
162. Stenson, W.F., and Lobos, E. 1982. Sulfasalazine inhibits the synthesis of chemotactic lipids by neutrophils. J Clin Invest 69:494-497.
163. Nielsen, O.H., Bukhave, K., Elmgreen, J., and Ahnfelt-Ronne, I. 1987. Inhibition of 5-lipoxygenase pathway of arachidonic acid metabolism in human neutrophils by sulfasalazine and 5-aminosalicylic acid. Dig Dis Sci 32:577-582.
164. Allgayer, H., and Stenson, W.F. 1988. A comparison of effects of sulfasalazine and its metabolites on the metabolism of endogenous vs. exogenous arachidonic acid.
167. Peskar, B.M., Dreyling, K.W., Peskar, B.A., May, B., and Goebell, H. 1986. Enhanced
167. Peskar, B.M., Dreyling, K.W., Peskar, B.A., May, B., and Goebell, H. 1986. Enhanced