Leukotrienes in Airways and Blood Vessels

  • P. J. Piper
Conference paper
Part of the Bayer AG Centenary Symposium book series (BAYER)

Abstract

Hydrolysis of phospholipids of the cell membrane by phospholipases gives rise to a wealth of extremely potent biologically active substances that may have important roles in human disease. One of the most recent outstanding biochemical and pharmacological achievements has been the elucidation of the metabolism of arachidonic acid and the discovery that it is the precursor of prostaglandins, prostacyclin, leukotrienes (LTs) and lipoxins. The possibility that there are yet more metabolites of this 20:4 fatty acid with high biological activity cannot be ruled out.

Keywords

Glutathione Histamine Prostaglandin Acetyl Indomethacin 

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References

  1. 1.
    Allan G, Levi R (1981) Thromboxane and prostacyclin release during cardiac immediate hypersensitivity reactions in vitro. J Pharmacol Exp Ther 217: 57–61Google Scholar
  2. 2.
    Arm JP, Spur BW, Lee TH (1987) Leukotriene E4 (LTE4) enhances airway histamine responsiveness in asthmatic subjects ( Abstract ). Thorax 42: 220Google Scholar
  3. 3.
    Augstein J, Farmer JB, Lee TB, Sheard P, Tattersall ML (1973) Selective inhibition of slow-reacting substance of anaphylaxis. Nature [New Biol] 245: 215–217CrossRefGoogle Scholar
  4. 4.
    Barnes NC, Piper PJ (1986) The actions of leukotrienes in human lung in vitro and in vivo. In: Piper PJ (ed) The leukotrienes: their biological significance. Raven, New York, pp 199–212Google Scholar
  5. 5.
    Barnes NC, Piper PJ, Costello JF (1984) Comparative actions of inhaled leukotriene C4, leukotriene D4 and histamine in normal human subjects. Thorax 39: 500–504PubMedCrossRefGoogle Scholar
  6. 6.
    Barnes NC, Piper PJ, Costello JF (1987) The effect of an oral leukotriene antagonist L649,923 on histamine and leukotriene D4-induced bronchoconstriction in normal man. J Allergy Clin Immunol 79: 816–818PubMedCrossRefGoogle Scholar
  7. 7.
    Barnett K, Piper PJ (1985) The release of leukotrienes from large and small airways of guinea pig and man ( Abstract ). Br J Pharmacol 86: 642PGoogle Scholar
  8. 8.
    Bernstrom K, Hammarstrom S (1988) Metabolism of LTE4 by rat tissues: formation of N-acetyl leukotriene E4. Arch Biochem Biophys 224: 486–491Google Scholar
  9. 9.
    Britton JR, Fuller RW, Taylor GW, Barnes PJ, Dollery CT (1988) Bronchial reactivity is not increased after inhalation of leukotriene B4 and prostaglandin D2. Br J Pharmacol (in press)Google Scholar
  10. 10.
    Britton JR, Hanley SP, Tattersfield AE (1987) The effect of an oral leukotriene D4 antagonist L-649,923 on the response to inhaled antigen in asthma. J Allergy Clin Immunol 79: 811PubMedCrossRefGoogle Scholar
  11. 10.
    Brocklehurst WE (1960) The release of histamine and formation of a slow-reacting substance (SRS-A) during anaphylactic shock. J Physiol (Lond) 151: 416–435Google Scholar
  12. 12.
    Buckner CK, Krell RD, Laravuso RB, Coursin DB, Bernstein PR, Will JA (1986) Pharmacological evidence that human intralobar airways do not contain different receptors that mediate contractions to leukotriene C4 and leukotriene D4. J Pharmacol Exp Ther 237: 558–562PubMedGoogle Scholar
  13. 13.
    Conroy DM, Piper PJ, Samhoun MN (1987) The effect of N-acetyl leukotriene E4 on guinea-pig airway smooth muscle in vitro ( Abstract ). Br J Pharmacol 91: 365PGoogle Scholar
  14. 14.
    Dahlén SE, Hansson G, Hedqvist P, Bjorck T, Granström E, Dahlen B (1983) Allergen challenge of lung tissue from asthmatics elicits bronchial contraction that correlates with the release of leukotrienes C4, D4 and E4. Proc Natl Acad Sci USA 80: 1712–1716PubMedCrossRefGoogle Scholar
  15. 15.
    Evans JM, Barnes NC, Zakrzewski JT, Glenny HP, Piper PJ, Costello JF (1988) Effects of an inhaled leukotriene (LT) antagonist, SKF 104,353-Z2 on LTD4- and histamine-induced bronchoconstriction in normal man. Br J Pharmacol 26: 677–678Google Scholar
  16. 16.
    Evans JM, Barnes NC, Piper PJ, Costello JF (1988) The effect of a single dose of an inhaled leukotriene antagonist L-648,051 in mild asthma. Br J Clin Pharmacol Thorax 43 (10): 836Google Scholar
  17. 17.
    Fleisch JH, Rinkema LE, Whitesitt CA, Marshall WS (1986) Pharmacologic antagonism of leukotriene-mediated events. In: Piper PJ (ed) The leukotrienes — their biological significance. Raven, New York, pp 109–125Google Scholar
  18. 18.
    Fleisch JH, Cloud ML, Marshall WS (1988) A brief review of preclinical and clinical studies with LY-171,883 and some comments on newer cysteinyl leukotriene receptor antagonists. Ann NY Acad Sci 524: 356–368PubMedCrossRefGoogle Scholar
  19. 19.
    Hay DWP, Muccitelli RM, Tucker SS, Vickery-Clark LM, Torphy TJ (1987) Pharmacological profile of SKF 104,353 a novel, potent and selective peptidoleukotriene receptor antagonist in guinea-pig and human airways. J Pharmacol Exp Ther 243: 474–481PubMedGoogle Scholar
  20. 20.
    Holroyde MC, Altounyan REC, Cole AH, Dixon M, Elliott EV (1981) Bronchoconstriction produced in man by leukotrienes C and D. Lancet II: 17–18Google Scholar
  21. 21.
    Krell RD, Tsai BS, Berdoulay A, Barbone M, Giles RE (1983) Heterogeneity of leukotriene receptors in guinea-pig trachea. Prostaglandins 25: 171–178PubMedCrossRefGoogle Scholar
  22. 22.
    Jones TR, Zamboni R, Belley M, Champion E, Charette L, Ford-Hutchinson AW, Frenette R, Gauthier J-Y, Leger S, Masson T, McFarlance CS, Piechonta H, Rotach J, Williams H, Young RM, DeHaven RM, Pong SS (1989) Pharmacology of L-660,711 (MK-571): a novel, potent and selective LTD4 receptor antagonist. Can J Physiol Pharmacol 67: 17–28PubMedCrossRefGoogle Scholar
  23. 23.
    Krell RD, Giles RE, Yee YK, Snyder DW (1987) In vivo pharmacology of ICI 198,615 a novel potent and selective peptide leukotriene antagonist. J Pharmacol Exp Ther 243: 557–564PubMedGoogle Scholar
  24. 24.
    Letts LG, Piper PJ (1982) The actions of leukotrienes C4 and D4 on guinea-pig isolated hearts. Br J Pharmacol 76: 169–176PubMedGoogle Scholar
  25. 25.
    Levi R (1972) Effects of exogenous and immunologically released histamine on the isolated heart: a quantitative comparison. J. Pharmacol Exp Ther 182: 227–238PubMedGoogle Scholar
  26. 26.
    Liebig R, Bernauer W, Peskar BA (1975) Prostaglandin, slow-reacting substance and histamine release from anaphylactic guinea-pig hearts and its pharmacological modification. Naunyn Schmiedebergs Arch Pharmacol 289: 65–76PubMedCrossRefGoogle Scholar
  27. 27.
    Marone G, Giordano A, Cirillo R, Triggiani M, Vigorito C (1988) Cardiovascular and metabolic effects of peptide leukotrienes in man. Ann NY Acad Sci 524: 321–333PubMedCrossRefGoogle Scholar
  28. 28.
    O’Driscoll BRC, Kay AB (1982) Leukotrienes and lung disease. Thorax 37: 241PubMedCrossRefGoogle Scholar
  29. 29.
    Phillips GD, Rafferty P, Holgate ST (1987) LY-171883 as an oral leukotriene D4 antagonist in non-asthmatic subjects. Thorax 42: 723Google Scholar
  30. 30.
    Piomelli D, Feinmark SJ, Cannon PJ (1987) Leukotriene biosynthesis by canine and human coronary arteries. J Pharmacol Exp Ther 241: 763–770PubMedGoogle Scholar
  31. 31.
    Piper PJ (1983) Pharmacology of leukotrienes. Br Med Bull 39: 255–259PubMedGoogle Scholar
  32. 32.
    Piper PJ (1984) Formation and actions of leukotrienes. Phys Rev 64: 744–761Google Scholar
  33. 33.
    Piper PJ, Levene S (1987) Human umbilical arteries and veins: generation of leukotrienes and responses to exogenous leukotrienes. Biol Neonate 52: 9–15PubMedCrossRefGoogle Scholar
  34. 34.
    Piper PJ, Samhoun MN (1981) The mechanism of action of leukotrienes C4 and D4 in guinea-pig isolated perfused lung and parenchymal strips of guinea pig, rabbit and rat. Prostaglandins 21: 793–803PubMedCrossRefGoogle Scholar
  35. 35.
    Piper PJ, Samhoun MN (1982) Stimulation of arachidonic acid metabolism and generation of thromboxane A2 by leukotrienes 134, C4 and D4 in guinea-pig lung in vitro. Br J Pharmacol 77: 267–275PubMedGoogle Scholar
  36. 36.
    Piper PJ, Samhoun MN (1987) Leukotrienes. Br Med Bull 43: 297–311Google Scholar
  37. 37.
    Piper PJ, Stewart AG (1986) Coronary vasoconstriction in the rat, isolated perfused heart induced by platelet-activating factor is mediated by leukotriene C4. Br J Pharmacol 88: 595–605PubMedGoogle Scholar
  38. 38.
    Piper PJ, Letts LG, Galton SA (1983) Generation of a leukotriene-like substance from porcine vascular and other tissues. Prostaglandins 25: 591–599PubMedCrossRefGoogle Scholar
  39. 38.
    Piper PJ, Letts LG, Galton SA (1983) Generation of a leukotriene-like substance from porcine vascular and other tissues. Prostaglandins 25: 591–599PubMedCrossRefGoogle Scholar
  40. 40.
    Piper PJ, Antoniw JW, Stanton AWB (1988) Release of leukotrienes from porcine and human blood vessels by immunological and non-immunological stimuli. Ann NY Acad Sci 524: 133–141PubMedCrossRefGoogle Scholar
  41. 41.
    Samhoun MN, Piper PJ (1984) Leukotriene F4: comparison of its pharmacological profile with that of the other cysteinyl-conatining leukotrienes in guinea-pig ileum and lung parenchyma in vitro. Prostaglandins 28: 623–628CrossRefGoogle Scholar
  42. 42.
    Samuelsson B (1983) Leukotrienes: a new class of mediators of immediate hypersensitivity reactions and inflammation. Adv Prostaglandin Thromboxane Leukotriene Res 11: 1–13Google Scholar
  43. 43.
    Yaacob HB, Piper PJ (1988) The effects of PAF-antagonist WEB 2086 on Paf-induced responses in guinea-pig isolated hearts and in cardiac anaphylaxis. Br J Pharmacol (in press)Google Scholar
  44. 44.
    Yaacob HB, Piper PJ (1988) Inhibition of leukotriene release in anaphylactic guinea-pig hearts by a 5-lipoxygenase inhibitor, CGS 8515. Br J Pharmacol (in press)Google Scholar
  45. 45.
    Zakrzewski JT, Barnes NC, Costello JF, Piper PJ (1987) Lipid mediators in cystic fibrosis and chronic obstructive pulmonary disease. Am Rev Respir Dis 136: 779–782PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1989

Authors and Affiliations

  • P. J. Piper
    • 1
  1. 1.Department of Pharmacology, Hunterian InstituteRoyal College of SurgeonsLondonUK

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