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. 1984 Mar;81(3):465–473. doi: 10.1111/j.1476-5381.1984.tb10099.x

Mediators of arachidonic acid-induced contractions of indomethacin-treated guinea-pig airways: leukotrienes C4 and D4.

J F Burka, M H Saad
PMCID: PMC1986854  PMID: 6421354

Abstract

Arachidonic acid (AA) (66 microM) induced contractions of indomethacin-treated (8.4 microM) guinea-pig tracheal and lung parenchymal preparations. Mepacrine (210 microM) treatment did not affect the magnitude of contraction induced by AA. Normal and ovalbumin-sensitized tissues responded identically to AA, and released equivalent amounts of the contractile mediators. Nordihydroguaiaretic acid (100 microM) markedly reduced release of the contractile mediators and reduced AA-induced contractions of the airways. The mediators of AA-induced, calcium ionophore A23187-induced, and antigen-induced contraction of the trachea and lung parenchyma were purified and identified by reverse-phase high performance liquid chromatography to be leukotrienes C4 and D4, being present in an approximate ratio of 20:1. Mepacrine-treated trachea exhibited a smaller contractile response to stimuli (A23187 for normal tissues and ovalbumin for sensitized tissues). Addition of exogenous AA (66 microM) increased the magnitude of contraction, although not to the level observed on tissues not treated with mepacrine. There was no observable effect of AA on the response of mepacrine-treated parenchyma to the ionophore or antigen. It was concluded that (a) immunological sensitization does not alter AA metabolism via the lipoxygenase pathway in guinea-pig airways and (b) the mediators of AA-induced contraction are leukotrienes C4 and D4.

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Selected References

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  1. Borgeat P., Samuelsson B. Arachidonic acid metabolism in polymorphonuclear leukocytes: effects of ionophore A23187. Proc Natl Acad Sci U S A. 1979 May;76(5):2148–2152. doi: 10.1073/pnas.76.5.2148. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Burka J. F., Ali M., McDonald J. W., Paterson N. A. Immunological and non-immunological synthesis and release of prostaglandins and thromboxanes from isolated guinea pig trachea. Prostaglandins. 1981 Nov;22(5):683–691. doi: 10.1016/0090-6980(81)90207-0. [DOI] [PubMed] [Google Scholar]
  3. Burka J. F., Flower R. J. Effects of modulators of arachidonic acid metabolism on the synthesis and release of slow-reacting substance of anaphylaxis. Br J Pharmacol. 1979 Jan;65(1):35–41. doi: 10.1111/j.1476-5381.1979.tb17331.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Burka J. F., Paterson N. A. Evidence for lipoxygenase pathway involvement in allergic tracheal contraction. Prostaglandins. 1980 Apr;19(4):499–515. doi: 10.1016/s0090-6980(80)80001-3. [DOI] [PubMed] [Google Scholar]
  5. CONSTANTINE J. W. THE SPIRALLY CUT TRACHEAL STRIP PREPARATION. J Pharm Pharmacol. 1965 Jun;17:384–385. doi: 10.1111/j.2042-7158.1965.tb07688.x. [DOI] [PubMed] [Google Scholar]
  6. Drazen J. M., Austen K. F., Lewis R. A., Clark D. A., Goto G., Marfat A., Corey E. J. Comparative airway and vascular activities of leukotrienes C-1 and D in vivo and in vitro. Proc Natl Acad Sci U S A. 1980 Jul;77(7):4354–4358. doi: 10.1073/pnas.77.7.4354. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hamberg M., Samuelsson B. Prostaglandin endoperoxides. VII. Novel transformations of arachidonic acid in guinea pig lung. Biochem Biophys Res Commun. 1974 Dec 11;61(3):942–949. doi: 10.1016/0006-291x(74)90246-0. [DOI] [PubMed] [Google Scholar]
  8. Hanna C. J., Bach M. K., Pare P. D., Schellenberg R. R. Slow-reacting substances (leukotrienes) contract human airway and pulmonary vascular smooth muscle in vitro. Nature. 1981 Mar 26;290(5804):343–344. doi: 10.1038/290343a0. [DOI] [PubMed] [Google Scholar]
  9. Holroyde M. C., Altounyan R. E., Cole M., Dixon M., Elliott E. V. Bronchoconstriction produced in man by leukotrienes C and D. Lancet. 1981 Jul 4;2(8236):17–18. doi: 10.1016/s0140-6736(81)90254-3. [DOI] [PubMed] [Google Scholar]
  10. Jakschik B. A., Lee L. H. Enzymatic assembly of slow reacting substance. Nature. 1980 Sep 4;287(5777):51–52. doi: 10.1038/287051a0. [DOI] [PubMed] [Google Scholar]
  11. Jones T. R., Davis C., Daniel E. E. Pharmacological study of the contractile activity of leukotriene C4 and D4 on isolated human airway smooth muscle. Can J Physiol Pharmacol. 1982 May;60(5):638–643. doi: 10.1139/y82-087. [DOI] [PubMed] [Google Scholar]
  12. Lulich K. M., Mitchell H. W., Sparrow M. P. The cat lung strip as an in vitro preparation of peripheral airways: a comparison of beta-adrenoceptor agonists, autacoids and anaphylactic challenge on the lung strip and trachea. Br J Pharmacol. 1976 Sep;58(1):71–79. doi: 10.1111/j.1476-5381.1976.tb07694.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. MacGlashan D. W., Jr, Schleimer R. P., Peters S. P., Schulman E. S., Adams G. K., 3rd, Newball H. H., Lichtenstein L. M. Generation of leukotrienes by purified human lung mast cells. J Clin Invest. 1982 Oct;70(4):747–751. doi: 10.1172/JCI110670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Mathé A. A., Yen S. S., Sohn R., Hedqvist P. Release of prostaglandins and histamine from sensitized and anaphylactic guinea pig lungs--changes in cyclic AMP levels. Biochem Pharmacol. 1977 Feb 1;26(3):181–188. doi: 10.1016/0006-2952(77)90300-8. [DOI] [PubMed] [Google Scholar]
  15. Mencia-Huerta J. M., Hadji L., Benveniste J. Release of a slow-reacting substance from rabbit platelets. J Clin Invest. 1981 Dec;68(6):1586–1591. doi: 10.1172/JCI110413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mitchell H. W., Denborough M. A. The metabolism of arachidonic acid in the isolated tracheal and lung strip preparations of guinea-pigs. Lung. 1980;158(3):121–129. doi: 10.1007/BF02713714. [DOI] [PubMed] [Google Scholar]
  17. Mitchell H. W. Effect of ETYA and BW 755c on arachidonate-induced contractions in the guinea-pig isolated trachea. Br J Pharmacol. 1982 Aug;76(4):527–529. doi: 10.1111/j.1476-5381.1982.tb09250.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Morris H. R., Taylor G. W., Jones C. M., Piper P. J., Samhoun M. N., Tippins J. R. Slow reacting substances (leukotrienes): enzymes involved in their biosynthesis. Proc Natl Acad Sci U S A. 1982 Aug;79(16):4838–4842. doi: 10.1073/pnas.79.16.4838. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Morris H. R., Taylor G. W., Piper P. J., Tippins J. R. Structure of slow-reacting substance of anaphylaxis from guinea-pig lung. Nature. 1980 May 8;285(5760):104–106. doi: 10.1038/285104a0. [DOI] [PubMed] [Google Scholar]
  20. Piper P. J., Samhoun M. N. 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. 1981 May;21(5):793–803. doi: 10.1016/0090-6980(81)90236-7. [DOI] [PubMed] [Google Scholar]
  21. Piper P. J., Seale J. P. Non-immunological release of slow-reacting substance from guinea-pig lungs. Br J Pharmacol. 1979 Sep;67(1):67–72. [PMC free article] [PubMed] [Google Scholar]
  22. Piper P. J., Tippins J. R., Morris H. R., Taylor G. W. Arachidonic acid metabolism and SRS-A. Agents Actions Suppl. 1979;(4):37–48. [PubMed] [Google Scholar]
  23. Saad M. H., Burka J. F. Effects of immunological sensitization on the responses and sensitivity of guinea pig airways to bronchoconstrictors. Modulation by selective inhibition of arachidonic acid metabolism. Can J Physiol Pharmacol. 1983 Aug;61(8):876–887. doi: 10.1139/y83-133. [DOI] [PubMed] [Google Scholar]
  24. Saad M. H., Wilson M. A., Burka J. F. Release of leukotriene C4 from guinea pig trachea. Prostaglandins. 1983 May;25(5):741–752. doi: 10.1016/0090-6980(83)90128-4. [DOI] [PubMed] [Google Scholar]
  25. Saeed S. A., Mitchell M. D. Arachidonate lipoxygenase activity in human fetal lung. Eur J Pharmacol. 1982 Mar 12;78(3):389–391. doi: 10.1016/0014-2999(82)90047-4. [DOI] [PubMed] [Google Scholar]
  26. Samuelsson B., Hammarström S., Murphy R. C., Borgeat P. Leukotrienes and slow reacting substance of anaphylaxis (SRS-A). Allergy. 1980 Jul;35(5):375–381. doi: 10.1111/j.1398-9995.1980.tb01782.x. [DOI] [PubMed] [Google Scholar]
  27. Weichman B. M., Hostelley L. S., Bostick S. P., Muccitelli R. M., Krell R. D., Gleason J. G. Regulation of the synthesis and release of slow-reacting substance of anaphylaxis from sensitized monkey lung. J Pharmacol Exp Ther. 1982 May;221(2):295–302. [PubMed] [Google Scholar]
  28. Yen S. S. Inhibition of arachidonic acid-induced contraction of guinea pig lung strips. Prostaglandins. 1981 Aug;22(2):183–194. doi: 10.1016/0090-6980(81)90033-2. [DOI] [PubMed] [Google Scholar]

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