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Leukotriene D4 potentiates histamine-induced bronchoconstriction in guinea-pigs

  • Histamine and Kinins
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Abstract

Histamine concentration-response curves performed on isolated airways smooth muscle preparations were unaffected by threshold constrictor concentrations of LTD4 (194±34 pM for parenchymal strips and 1940±480 pM for isolated trachea, respectively). In contrast, LTD4, when administered between 2 and 60 s beforehand, potentiated bronchoconstrictor responses to histamine in anaesthetized, artificially ventilated guinea-pigs. Doses of LTD4, which did not produce direct effects on airways resistance, potentiated histamine-induced bronchoconstriction to a lesser degree than those having small direct effects. This potentiation was prevented by bilateral vagotomy. In addition, the antagonists atropine (100 μg/kg), FPL55712 (5 mg/kg) and indomethacin (1 mg/kg) effectively prevented the interaction. It is suggested that the interaction between LTD4 and histamine involves a specific leukotriene receptor, possibly linked to the generation of a cyclo-oxygenase metabolite and requires intact cholinergic innervation of airways smooth muscle. Furthermore, these results are consistent with the hypothesis that LTD4 may be a mediator of bronchial hyperreactivity.

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References

  1. H.R. Morris, C.W. Taylor, P.J. Piper andJ.R. Tippins,Structure of slow reacting substance of anaphylaxis from guinea-pig lung, Nature285, 104–106 (1980).

    Google Scholar 

  2. W.E. Brocklehurst,The release of histamine and formation of a slow reacting substance (SRS-A) during anaphylactic shock. J. Physiol., Lond.151, 416–435 (1980).

    Google Scholar 

  3. J.M. Drazen, K.F. Austen, R.A. Lewis, D.A. Clark, G. Goto, A. Marfat andE.J. Corey,Comparative airway and vascular activities of leukotrienes C-1 and D in vivo and in vitro, Proc. natn. Acad. Sci. USA77, 4534–4538 (1980).

    Google Scholar 

  4. P. Hedqvist, S. Dahlen, L. Gustafsson, S. Hammarstrom andB. Samuelsson,Biological profile of leukotrienes C 4 and D 4 , Acta physiol. scand.110, 331–333 (1980).

    Google Scholar 

  5. S. Dahlen, P. Hedqvist, S. Hammarstrom andB. Samuelsson,Leukotrienes are potent constrictors of human bronchi, Nature288, 484–486 (1980).

    Google Scholar 

  6. C.J. Hanna, M.K. Bach, P.D. Pare andR.R. Schellenberg,Slow-reacting substances (leukotrienes) contract human airway and pulmonary vascular smooth muscle in vitro, Nature290, 343–344 (1981).

    Google Scholar 

  7. T.R. Jones, C. Davis andE.E. Daniel,Pharmacological study of the contractile activity of leukotriene C 4 and D 4 on isolated human airway smooth muscle, Can. J. Physiol. Pharmac.60, 638–643 (1982).

    Google Scholar 

  8. J. Augstein, J.B. Farmer, T.B. Lee, P. Sheard andM.L. Tattersal,Selective inhibitor of slow reacting substance of anaphylaxis, Nature245, 215–217 (1973).

    Google Scholar 

  9. P.J. Piper andM.N. Samhoun,The mechanism of action of leukotrienes C 4 and D 4 in guinea-pig isolated perfused lung and parenchymal strips of guinea-pig, rabbit and rat, Prostaglandins21, 793–803 (1981).

    Google Scholar 

  10. J.M. Drazen, R.A. Lewis, S.I. Wasserman, R.P. Orange andK.F. Austen,Differential effects of a partially purified preparation of a slow reacting substance of anaphylaxis on guinea-pig tracheal spirals and parenchymal strips, J. clin. Invest.63, 1–5 (1979).

    Google Scholar 

  11. J.A. Nadel,Pathophysiology of asthma: neural effects on airway smooth muscle, submucosal glands, breathing and cough, Prog. Respir. Res.14, 1–8 (1980).

    Google Scholar 

  12. A.A. Mathé, P. Hedqvist, A. Holmgren andH. Svanborg,Bronchial hyperreactivity to prostaglandin F and histamine in patients with asthma, Br. med. J.1, 193–196 (1973).

    Google Scholar 

  13. Bo.G. Simonsson,Bronchial hyperreactivity, Eur. J. Respir. Dis.61, Suppl. 108, 21–28 (1980).

    Google Scholar 

  14. M.J. Holtzman, J.R. Sheller, M. Dimeo, J.A. Nadel andH.A. Boushey,Effect of ganglionic blockade on bronchial reactivity in atopic subjects, Am. Rev. resp. Dis.122, 17–25 (1980).

    Google Scholar 

  15. J.W. Constantine,The spirally cut tracheal strip preparation, J. Pharm. Pharmac.17, 384–385 (1965).

    Google Scholar 

  16. J. Emmerson andD. Mackay,The zig-zag tracheal strip, J. Pharm. Pharmac.31, 798 (1979).

    Google Scholar 

  17. K.M. Lulich, M.W. Mitchell andM.P. Sparrow,The cat lung strip as an in vitro preparation of peripheral airways: a comparison of β-adrenoceptor agonists, autacoids and anaphylactic challenge on the lung strip and trachea, Br. J. Pharmac.58, 71–79 (1976).

    Google Scholar 

  18. J.M. Drazen andM.W. Schneider,Comparative responses of tracheal spirals and parenchymal strips to histamine and carbachol in vitro, J. clin. Invest.61, 1441–1447 (1978).

    Google Scholar 

  19. J.T. Van Rossum,Cumulative Dose-response Curves II. Technique for the making of dose-response curves in isolated organs and the evaluation of drug parameters, Archs int. Pharmacodyn. Thér.143, 299–330 (1963).

    Google Scholar 

  20. R. Levi andJ.A. Burke,Cardiac anaphylaxis: SRS-A potentiates and extends the effects of released histamine, Eur. J. Pharmac.62, 41–49 (1980).

    Google Scholar 

  21. B.B. Vargaftig, J. Lefort andR.C. Murphy,Inhibition by aspirin of bronchoconstriction due to leukotrienes C 4 and D 4 in the guinea-pig, Eur. J. Pharmac.72, 417–418 (1981).

    Google Scholar 

  22. S.R. Sampson andE.H. Vidruk,Chemical stimulation of rapidly adapting receptors in the airways, Adv. expl Med. Biol.99, 281–290 (1978).

    Google Scholar 

  23. A. Welton, W.C. Hope, L.D. Tobias andJ.G. Hamilton,Inhibition of antigen-induced histamine release and thromboxane synthase by FPL 55712, a specific SRS-A antagonist? Biochem. Pharmac.30, 1378–1382 (1981).

    Google Scholar 

  24. G. Folco, G. Hansson andE. Granstrom,Leukotriene C 4 stimulates TXA 2 formation in isolated sensitized guinea-pig lungs, Biochem. Pharmac.30, 2491–2493 (1981).

    Google Scholar 

  25. G. Folco, C. Omini, G. Rossoni, T. Vigano andF. Berti,Anticholinergic agents prevent guinea-pig airway constriction induced by histamine, bradykinin and leukotriene C 4 : relationship to circulating TXA 2 , Eur. J. Pharmac.78, 159–165 (1982).

    Google Scholar 

  26. F. Berti, G.C. Folco, A. Giachetti, S. Malandrino, C. Omini andT. Vigano,Atropine inhibits thromboxane A 2 generation in isolated lungs of the guinea-pig, Br. J. Pharmac.68, 467–472 (1980).

    Google Scholar 

  27. J.E. Mills andJ.G. Widdicombe,Role of the vagus nerves in anaphylaxis and histamine-induced bronchoconstrictions in guinea-pigs, Br. J. Pharmac.39, 724–731 (1970).

    Google Scholar 

  28. V. Popa, J.S. Douglas andA. Bouhuys,Airway responses to histamine, acetylcholine and propranolol in anaphylactic hypersensitivity in guinea-pigs, J. All. Clin. Immunol.51, 344–356 (1973).

    Google Scholar 

  29. D.Y.C. Yu, S.P. Galant andW.M. Gold,Inhibition of antigen-induced bronchoconstriction by atropine in asthmatic patients, J. appl. Physiol.32, 823–828 (1972).

    Google Scholar 

  30. J.A. Nadel, H. Salem, B. Tamplin andY. Tokiwa,Mechanism of bronchoconstriction during inhalation of sulphur dioxide. J. appl. Physiol.20, 164–167 (1965).

    Google Scholar 

  31. A.G. Stewart, D.C. Thompson andM.R. Fennessy, Interaction of Leukotriene D4 and histamine on bronchomotor tone in the guinea-pig, J. Pharm. Pharmac.35, 755–756 (1983).

    Google Scholar 

  32. M. Griffin, J.W. Weiss, A.G. Leitch, E.R. McFadden, E.J. Corey, K.F. Austen andJ.M. Drazen.Effects of leukotriene D on the airways in asthma, New Engl. J. Med.308, 436–439 (1983).

    Google Scholar 

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Stewart, A.G., Thompson, D.C. & Fennessy, M.R. Leukotriene D4 potentiates histamine-induced bronchoconstriction in guinea-pigs. Agents and Actions 15, 146–152 (1984). https://doi.org/10.1007/BF01972341

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