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Involvement of capsaicin-sensitive afferent neurones in a vagal-dependent interaction between leukotriene D4 and histamine on bronchomotor tone

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Abstract

Leukotriene D4 (LTD4, 0.1–0.5 μg/kg, i.v.), administered 20 s before histamine (H, 1–4 μg/kg, i.v.), enhanced the bronchoconstrictor response to H by between 105 and 168%. Bilateral vagotomy, atropine or indomethacin each attenuated, whereas hexamethonium completely prevented, this enhancement. LTD4 failed to enhance the bronchoconstrictor effects of either acetylcholine (ACh) or electrical stimulation of the vagi. Capsaicin pretreatment reduced bronchoconstrictor responses to electrical stimulation of the vagi, but did not affect depressor responses. There was no interaction between LTD4 and H on bronchomotor tone in capsaicin-pretreated guinea-pigs. It is concluded that LTD4 enhances H-induced bronchoconstriction by a mechanism which involves an increased activity of efferent cholinergic nerves innervating the airways. However, the failure of LTD4 to enhance bronchoconstriction due to ACh or vagal stimulation, together with the prevention of the interaction between LTD4 and H by capsaicin-pretreatment, suggests that the site of the interaction may be on capsaicin-sensitive afferent neurones.

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References

  1. A.G. Stewart, D.C. Thompson andM.R. Fennessy,Interaction of leukotriene D 4 and histamine on bronchomotor tone in the guinea-pig, J. Pharm. Pharmac.35, 755–756 (1983).

    Google Scholar 

  2. A.G. Stewart, D.C. Thompson andM.R. Fennessy,Leukotriene D 4 potentiates histamine-induced bronchoconstriction in guinea-pigs, Agents and Actions (in press) (1984).

  3. B.R. Creese andM.K. Bach,Hyperreactivity of airways smooth muscle produced in vitro by leukotrienes, Prostaglandins, Leuk. Med.11, 161–169 (1983).

    Google Scholar 

  4. 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).

    PubMed  Google Scholar 

  5. M.C. Holroyde, R.E.C. Altounyan, M. Cole, M. Dixon andE.V. Elliott,Bronchoconstriction produced in man by leukotrienes C and D, Lancetii, 17–18 (1981).

    Article  Google Scholar 

  6. A. Cartier, N.C. Thomson, P.A. Frith, R. Roberts andF.E. Hargreave,Allergen-induced increase in bronchial responsiveness to histamine: relationship to the late asthmatic response and change in airway calibre, J. Allergy & Clin. Immunol.70, 170–177 (1982).

    Google Scholar 

  7. M.W. McCulloch, C. Proctor andM.J. Rand,Evidence for an adrenergic homeostatic bronchodilator reflex mechanism, Eur. J. Pharmac.2, 214–233 (1967).

    Article  Google Scholar 

  8. R. Gamse, A. Wax, R.E. Zigmond andS.E. Leeman,Immunoreactive substance P in sympathetic ganglia: distribution and sensitivity towards capsaicin, Neuroscience6, 437–441 (1981).

    Article  PubMed  Google Scholar 

  9. J.M. Lundberg andA. Saria,Bronchial smooth muscle contraction induced by stimulation of capsaicin-sensitive sensory neurones, Acta physiol. scand.116, 473–476 (1982).

    PubMed  Google Scholar 

  10. M.O. Amdur andJ. Mead,Mechanics of respiration in unanaesthetized guinea-pigs, Am. J. Physiol.192, 364–368 (1958).

    PubMed  Google Scholar 

  11. L. Diamond,Potentiation of bronchomotor responses by beta adrenergic antagonists, J. Pharmac. exp. Ther.181, 434–445 (1972).

    Google Scholar 

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

    Article  PubMed  Google Scholar 

  13. M.K. Benson,Bronchial hyperreactivity, Br. J. Dis. Chest69, 227–239 (1975).

    Article  PubMed  Google Scholar 

  14. J. Orehek,The concept of airway ‘sensitivity’ and ‘reactivity’, Eur. J. Resp. Dis.64, (Suppl. 131) 27–48 (1983).

    Google Scholar 

  15. 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, 4354–4358 (1980).

    Google Scholar 

  16. C. Advenier, J. Cerrina, P. Duroux, A. Floch, J. Pradel andA. Renier,Sodium cromoglycate, verapamil and nicardipine antagonism to leukotriene D 4 bronchoconstriction, Br. J. Pharmac.78, 301–306 (1983).

    Google Scholar 

  17. W.E. Lux, G. Feuerstein andA.I. Faden,Alteration of leukotriene D 4 hypotension by thyrotropin releasing hormone, Nature302, 822–824 (1983).

    Article  PubMed  Google Scholar 

  18. J.S. Douglas, M.W. Dennis, P. Ridgway andA. Bouhuys,Airway constriction in guinea-pigs: interaction of histamine and autonomic drugs, J. Pharmac. exp. Ther.184, 169–179 (1973).

    Google Scholar 

  19. J.M. Drazen andK.F. Austen,Atropine modification of the pulmonary effects of chemical mediators in the guinea-pig, J. appl. Physiol.38, 834–838 (1975).

    PubMed  Google Scholar 

  20. M.C. Holroyde andD.M. Jackson,Effect of leukotrienes (LTs) on pulmonary function and lung irritant receptors in cats and dogs, Br. J. Pharmac.79, 217P (1983).

  21. H.G. Johnson, M.C. McNee, M.A. Johnson andM.D. Miller.Leukotriene C 4 and dimethylphenylpiperazinium-induced responses in canine airway tracheal muscle contraction and fluid secretion, Int. Archs Allergy appl. Immun.71, 214–218 (1983).

    Google Scholar 

  22. A.S. Paintal,The nature and effects of sensory inputs into the respiratory centers, Fedn. Proc.36, 2428–2432 (1977).

    Google Scholar 

  23. H.M. Coleridge, J.C.G. Coleridge, K.H. Ginzel, D.G. Baker, R.B. Banzett andM.A. Morrison,Stimulation of ‘irritant’ receptors and afferent C-fibres in the lungs by prostaglandins, Nature264, 451–453 (1976).

    PubMed  Google Scholar 

  24. M. Dixon, D.M. Jackson andI.M. Richards,The action of sodium cromoglycate on ‘C’ fibre endings in the dog lung, Br. J. Pharmac.70, 11–13 (1980).

    Google Scholar 

  25. M. Otsuka andS. Konishi,Substance P—the first peptide neurotransmitter? TINS,6, 317–320 (1983).

    Google Scholar 

  26. G. Terenghi, G.P. McGregor, S. Bhuttacharji, J. Wharton, S.R. Bloom andJ.M. Polak.Vagal origin of substance P-containing nerves in the guinea-pig lung, Neurosci. Lett.36, 229–236 (1983).

    Article  PubMed  Google Scholar 

  27. R. Gamse, F. Lembeck andA.C. Cuello,Substance P in the vagus nerve, Naunyn-Schmiedebergs Arch. Pharmak.306, 37–44 (1979).

    Article  Google Scholar 

  28. J.-A. Karlsson andC.G.A. Persson,Evidence against vasoactive intestinal polypeptide (VIP) as a dilator and in favour of substance P as a constrictor in airway neurogenic responses, Br. J. Pharmac.79, 634–636 (1983).

    Google Scholar 

  29. J.M. Lundberg, A. Saria, E. Brodin, S. Rosell andK. Folkers,A substance P antagonist inhibits vagally-induced increase in vascular permeability and bronchial smooth muscle contraction in the guinea-pig, Proc. Natn. Acad. Sci. USA80, 1120–1124 (1983).

    Google Scholar 

  30. 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).

    Article  Google Scholar 

  31. 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).

    PubMed  Google Scholar 

  32. S.-E. Dahlen,Pulmonary effects of leukotrienes, Acta physiol. scand. (Suppl. 512) (1983).

  33. R. Hamel, P. Masson, A.W. Ford-Hutchinson, T.R. Jones, G. Brunet andH. Piechuta,Differing mechanisms for leukotriene D 4-induced bronchoconstriction in guinea-pigs following intravenous and aerosol administration, Prostaglandins,24, 419–432 (1982).

    Article  PubMed  Google Scholar 

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  1. Department of Pharmacology, University of Melbourne, 3052, Parkville, Victoria, Australia

    A. G. Stewart, D. C. Thompson & M. R. Fennessy

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  2. D. C. Thompson
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  3. M. R. Fennessy
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Stewart, A.G., Thompson, D.C. & Fennessy, M.R. Involvement of capsaicin-sensitive afferent neurones in a vagal-dependent interaction between leukotriene D4 and histamine on bronchomotor tone. Agents and Actions 15, 500–508 (1984). https://doi.org/10.1007/BF01966763

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