Agents and Actions

, Volume 43, Issue 3–4, pp 176–178 | Cite as

Inhibition of arachidonic acid cyclo-oxygenase and lipoxygenase activities of leukocytes by indomethacin and compound BW755C

  • R. W. Randall
  • K. E. Eakins
  • G. A. Higgs
  • J. A. Salmon
  • J. E. Tateson
Article

Abstract

Arachidonic acid is metabolized via two pathways in leukocytes: cyclo-oxygenase, leading to the stable prostaglandins, and lipoxygenase, leading to hydroxyacids. Indomethacin inhibits the cyclo-oxygenase selectively, whereas compound BW755C (3-amino-1-(m-(trifluoromethyl)phenyl)-2-pyrazoline) inhibits both pathways equally. This offers a possible explanation for the differing activities of these two compounds in inflammatory models in vivo. The patterns of product inhibition by the two compounds support the suggestion that 11-HETE (hydroxy-eicosatetraenoic acid) and 15-HETE can arise by incomplete operation of the cyclo-oxygenase pathway.

Keywords

Phenyl Prostaglandin Arachidonic Acid Indomethacin Trifluoromethyl 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. [1]
    J.R. Vane,Inhibition of Prostaglandin Synthesis as a Mechanism of Action for the Aspirin-like Drugs, Nature231, 232–235 (1971).PubMedGoogle Scholar
  2. [2]
    P. Borgeat, M. Hamberg andB. Samuelsson,Transformation of Arachidonic Acid and Dihomolinolenic acid by polymorphonuclear leukocytes, J. Biol. Chem.251, 7816–7820 (1976).PubMedGoogle Scholar
  3. [3]
    R.C. Murphy, S. Hammarström andB. Samuelsson,Leukotriene C: A Slow-Reacting Substance from Murine Mastocytoma Cells. Proc. natn. Acad. Sci. USA76, 4275–4279 (1979).Google Scholar
  4. [4]
    S.R. Turner, J.A. Tainer andW.S. Lynn,Biogenesis of Chemotactic Molecules by the Arachidonate Lipoxygenase System of Platelets, Nature257, 680–681 (1975).PubMedGoogle Scholar
  5. [5]
    E.J. Goetzl, A.R. Brash, J.A. Oates andW.C. Hubbard,Functional Determinants of the Monohydroxy Eicosatetraenoic Acids (HETEs) which Stimulate Human Neutrophil and Eosinophil Chemotaxis, Fedn. Proc.38, 1085 (1979).Google Scholar
  6. [6]
    K.E. Eakins, G.A. Higgs, S. Moncada, K.G. Mugridge andJ.R. Vane.The Effects of Indomethacin and BW755C on Leukocyte Migration and Prostaglandin Production in Carrageenin-Induced Inflammation, Br. J. Pharmac.69, 270P-271P (1980).Google Scholar
  7. [7]
    M.I. Siegel, R.T. McConnell, N.A. Porter, J.L. Selph, J.F. Truax, R. Vinegar andP. Cuatrecasas,Aspirin-like Drugs Inhibit Arachidonic Acid Metabolism via Lipoxygenase and Cyclo-Oxygenase in Rat Neutrophils from Carrageenin Pleural Exudates, Biochem. Biophys. Res. Commun.92, 688–695 (1980).PubMedGoogle Scholar

Copyright information

© Birkhäuser Verlag 1994

Authors and Affiliations

  • R. W. Randall
    • 1
  • K. E. Eakins
    • 1
  • G. A. Higgs
    • 1
  • J. A. Salmon
    • 1
  • J. E. Tateson
    • 1
  1. 1.Department of Pharmacology and Prostaglandin ResearchWellcome Research LaboratoriesBeckenhamUK

Personalised recommendations