Skip to main content
Log in

The effect of the neurokinin antagonist FK-224 on the cough response to inhaled capsaicin in a new model of guinea-pig eosinophilic bronchitis induced by intranasal polymyxin B

  • Research Paper
  • Published:
Clinical Autonomic Research Aims and scope Submit manuscript

Abstract

Eosinophilic bronchitis without asthma can cause a persistent non-productive cough which is resistant to bronchodilator therapy. To understand the mechanism of the cough in this disorder, an animal model of eosinophilic bronchitis was developed. Guinea-pigs were treated with transnasal administration of polymyxin B or saline twice a week for 3 weeks. The number of eosinophils in bronchoalveolar lavage fluid increased in polymyxin B-treated animals when compared with those treated with saline. In addition, histological examination showed that the number of eosinophils infiltrated into the tracheal epithelium increased; injury to the tracheal epithelium was greater in polymyxin B-treated animals. The numbers of coughs induced by saline and each concentration of capsaicin (10−18, 10−16, 10−14M) were greater in the polymyxin B-treated animals. FK-224 (a neurokinin receptor antagonist) decreased the heightened cough reflex in this animal model of eosinophilic bronchitis. These findings suggest that neuropeptides, and particularly neurokinins, are involved in the heightened cough receptor sensitivity in eosinophilic bronchitis without asthma. This has implications for better understanding of this disorder and its treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. McFadden ER Jr. Exertional dyspnea and cough as preludes to acute attacks of bronchial asthma.N Engl J Med 1975;292: 555–559.

    PubMed  Google Scholar 

  2. Fujimura M, Sakamoto S, Tamotsu M. Bronchodilator-resistive cough in atopic patients: bronchial reversibility and hyperresponsiveness.Intern Med 1992;31: 447–452.

    PubMed  Google Scholar 

  3. Gibson PG, Dolovich J, Denburg J, Ramsdale EH, Hargreave FE. Chronic cough: eosinophilic bronchitis without asthma.Lancet 1989;17: 1346–1348.

    Google Scholar 

  4. Ogawa H, Fujimura M, Matsuda T, Nakamura H, Kumabashiri I, Kitagawa S. Transient wheeze: eosinophilic broncho-bronchiolitis in acute eosinophilic pneumonia.Chest 1992;104: 493–496.

    Google Scholar 

  5. Pincus SH. Production of eosinophil-rich guinea pig peritoneal exudates.Blood 1978;52: 127–134.

    PubMed  Google Scholar 

  6. Davis WB, Husney RM, Mohammed BS, Pawluk LJ, Ackerman GA, Sagone AL. Activation and deactivation of guinea pig peritoneal eosinophils during chronic polymyxin B stimulation.J Leuko Biol 1989;45: 147–154.

    PubMed  Google Scholar 

  7. Sun X, Davis WB, Fukuda Y, Ferrans VJ, Crystal RG. Experimental polymyxin B-induced interstitial lung disease characterized by an accumulation of cytotoxic eosinophils in the alveolar structures.Am Rev Respir Dis 1985;131: 103–108.

    PubMed  Google Scholar 

  8. Laycock SM, Smith H, Spicer BA. Airway hyperreactivity and blood, lung and airway eosinophilia in rats treated with Sephadex particles.Int Arch Allergy Appl Immunol 1986;81: 363–367.

    PubMed  Google Scholar 

  9. Nogami M, Suko M, Okudaira H, Miyamoto T, Shiga J, Ito M, Kasuya S. Experimental pulmonary eosinophilia in mice by ascaris suum extract.Am Rev Respir Dis 1990;141: 1289–1295.

    PubMed  Google Scholar 

  10. Gleich GL, Loegering D. Selective stimulation and purification of eosinophils and nentrophils from guinea pig peritoneal fluids.J Clin Med 1973;85: 522–526.

    Google Scholar 

  11. Kohrogi H, Nadel JA, Malfroy B, Gorman C, Bridenbaugh R, Patton JS, Borson DB. Recombinant human enkephalinase (neutral endopeptidase) prevents cough induced by tachykinins in awake guinea pigs.J Clin Invest 1989;84: 781–786.

    PubMed  Google Scholar 

  12. Jones T, Masson P, Hamel R, Bruunet G, Holme G, Girard Y, Larue M, Rokach J. Biological activity of leukotriene sulfones on respiratory tissues.Prostaglandins 1982;24: 279.

    PubMed  Google Scholar 

  13. Fujimura M. Inhibitory effects of steroids on slow-reacting substance of anaphylaxis (SRS-A) mediated bronchoconstriction in the guinea pigin vivo.Jpn J Allergol 1983;32: 365–375.

    Google Scholar 

  14. Irwin RS, Corrao WM, Pratter MR. Chronic persistent cough in adult: the spectrum and frequency of causes and successful outcome of specific therapy.Am Rev Respir Dis 1981;123: 413–417.

    PubMed  Google Scholar 

  15. Nishi K, Fujimura M, Myou S, Ooka T, Matsuda T. The importance of eosinophilic inflammation of the airways in chronic nonproductive cough without asthma (abstract).Jpn J Allergol 1992;41: 302.

    Google Scholar 

  16. Widdicombe JG. Receptors in the trachea and bronchi of the cat.J Physiol 1954;123: 71–104.

    PubMed  Google Scholar 

  17. Coleridge HM, Coleridge JCG, Ginzel KH, Baker DG, Banzett RB, Morrison MA. Stimulation of ‘irritant’ receptors and afferent C-fibres in the lungs by prostaglandins.Nature 1976;264: 451–453.

    PubMed  Google Scholar 

  18. Barnes PJ, Belvisi MG, Rogers DF. Modulation of neurogenic inflammation: novel approaches to inflammatory disease.TIPS 1990;111: 185–189.

    Google Scholar 

  19. Barnes PJ. Asthma as an axon reflex.Lancet 1986; i: 242–245.

    Google Scholar 

  20. Jancsó N., Jancsó-Gábor A, Szolcsányi J. Direct evidence for neurogenic inflammation and its preventation by denervation and by pretreatment with capsaicin.Br J Pharmac Chemother 1967;31: 138–151.

    Google Scholar 

  21. Morimoto H, Murai M, Maeda Y, Yamaoka M, Nishikawa M, Kiyotoh Sumio, Fujii T. FK-224, a novel cyclopeptide substance P antagonist with NK, and NK2 receptor selectivity.J Pharmacol Exp Ther 1992;262: 398–402.

    PubMed  Google Scholar 

  22. Murai M, Morlmoto H, Maeda Y, Yamaoka M, Kiyotoh S, Nishikawa M, Fujii T. Effects of FK-224, a novel compound NK, and NK2 receptor antagonist, on airway constriction and airway edema induced by neurokinins and sensory nerve stimulation in guinea pigs.

  23. Dusser DJ, Umeno E, Graf PD, Djokic T, Borson DB, Nedel JA. Airway neutral endopeptidase-like enzyme modulates tachykinin-induced bronchoconstrictionin vivo.J Appl Physiol 1988;65: 2585–2591.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ogawa, H., Fujimura, M., Saito, M. et al. The effect of the neurokinin antagonist FK-224 on the cough response to inhaled capsaicin in a new model of guinea-pig eosinophilic bronchitis induced by intranasal polymyxin B. Clinical Autonomic Research 4, 19–28 (1994). https://doi.org/10.1007/BF01828834

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01828834

Key words

Navigation