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Airway epithelial cells modulate cholinergic neurotransmission in dog trachea

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Abstract

We investigated the effects of epithelial cells on excitatory cholinergic neurotransmission in dog trachea, to shed more light on the role of airway epithelial cells in regulating airway responsiveness. Airway epithelial cells were prepared by an enzymatic dissociation of the tracheal mucosa using protease-free collagenase. Tracheal smooth muscle contractions evoked by electrical field stimulation (EFS) or acetylcholine (ACh) were measured before and after the application of epithelial cells. Isolated and dispersed epithelial cells (3 × 105 cells/ml) suppressed the amplitude of the twitch-like contractions evoked by EFS in the combined presence of guanethidine sulfate (10−6 m) and indomethacin (10−5 m). In contrast, epithelial cells did not affect the contraction evoked by exogenously applied ACh. Atropine (10−6 m) or tetrodotoxin (10−7 m) abolished the contraction evoked by electrical field stimulation. These findings indicate that airway epithelial cells inhibit the excitatory neurotransmission of the vagus nerve, presumably by suppressing the release of ACh. Airway epithelial cells may therefore play an important role in regulating the response of smooth muscle.

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References

  1. Aizawa H, Chung KF, Leikauf GD, Ueki IF, Bethel RA, O'Byrne PM, Hirose T, Nadel JA (1985) Significance of thromboxane generation in ozone-induced airway hyperresponsiveness in dogs. J Appl Physiol 59:1918–1923

    Google Scholar 

  2. Aizawa H, Miyazaki N, Shigematsu N, Tomooka M (1988) A possible role of airway epithelium in modulating hyperresponsiveness. Br J Pharmacol 93:139–145

    Google Scholar 

  3. Barnes PJ, Cuss FM, Palmer JB (1985) The effect of airway epithelium on smooth muscle contractility in bovine trachea. Br J Pharmacol 86:685–691

    Google Scholar 

  4. Barnett K, Jacoby DB, Nadel JA, Lazarus SC (1988) The effects of epithelial cell supernatant on contractions of isolated canine tracheal smooth muscle. Am Rev Respir Dis 138:780–783

    Google Scholar 

  5. Boucher RC, Pare PD, Hogg JC (1979) Relationship between airway hyperreactivity and hyperpermeability in Ascaris-sensitive monkeys. J Allergy Clin Immunol 64:197–201

    Google Scholar 

  6. Boushey HA, Holtzman MJ, Sheller JR, Nadel JA (1980) Bronchial hyperreactivity. Am Rev Respir Dis 121:389–413

    Google Scholar 

  7. Butler GB, Adler KB, Evans JN, Morgan DW, Szarek JL (1987) Modulation of rabbit airway smooth muscle responsiveness by respiratory epithelium. Am Rev Respir Dis 135:1099–1104

    Google Scholar 

  8. Danser AHJ, van den Ende R, Lorenz RR, Flavahan NA, Vanhoutte PM (1987) Prejunctional β1-adrenoceptors inhibit cholinergic transmission in canine bronchi. J Appl Physiol 62:785–790

    Google Scholar 

  9. Empey DW, Laitinen LA, Jacobs L, Gold WM, Nadel JA (1976) Mechanisms of bronchial hyperreactivity in normal subjects after upper respiratory tract infection. Am Rev Respir Dis 113:131–139

    Google Scholar 

  10. Fabbri LM, Aizawa H, Alpert SE, Walters EH, O'Byrne PM, Gold BD, Holtzman MJ, Nadel JA (1984) Airway hyperresponsiveness and changes in cell counts in bronchoalveolar lavage after ozone exposure in dogs. Am Rev Respir Dis 129:288–291

    Google Scholar 

  11. Fernades LB, Preuss JMH, Paterson JW, Goldie RG (1990) Epithelium-derived inhibitory factor in human bronchus. Eur J Pharmacol 187:331–336

    Google Scholar 

  12. Fine JM, Gordon T, Sheppard D (1989) Epithelium removal alters responsiveness of guinea pig trachea to substance P. J Appl Physiol 66:232–237

    Google Scholar 

  13. Flavahan NA, Aarhus LL, Rimele TJ, Vanhoutte PM (1985) Respiratory epithelium inhibits bronchial smooth muscle tone. J Appl Physiol 58:834–838

    Google Scholar 

  14. Franconi GM, Rubinstein I, Levine EH, Ikeda S, Nadel JA (1990) Mechanical removal of airway epithelium disrupts mast cells and releases granules. Am J Physiol 259:L372-L377

    Google Scholar 

  15. Hay DWP, Muccitelli RM, Horstemeyer DL, Wilson KA, Raeburn JD (1987) Demonstration of the release of an epithelium-derived inhibitory factor from a novel preparation of guinea-pig trachea. Eur J Pharmacol 136:247–250

    Google Scholar 

  16. Holtzman MJ, Aizawa H, Nadel JA, Goetzl EJ (1983) Selective generation of leukotriene B4 by tracheal epithelial cells from dogs. Biochem Biophys Res Commun 114:1071–1076

    Google Scholar 

  17. Holtzman MJ, Fabbri JM, O'Byrne PM, Gold BD, Aizawa H, Walters EH, Alpert SE, Nadel JA (1983) Importance of airway inflammation for hyperresponsiveness induced by ozone. Am Rev Respir Dis 127:686–690

    Google Scholar 

  18. Inoue T, Ito Y, Takeda K (1984) Prostaglandin-induced inhibition of acetylcholine release from neuronal elements of dog tracheal tissue. J Physiol 349:553–570

    Google Scholar 

  19. Ito Y, Yoshitomi T (1988) Autoregulation of acetylcholine release from vagus nerve terminals through activation of muscarinic receptors in dog trachea. Br J Pharmacol 93:636–646

    Google Scholar 

  20. Laitinen LA, Heino M, Laitinen A, Kava T, Haahtela T (1985) Damage of the airway epithelium and bronchial reactivity in patients with asthma. Am Rev Respir Dis 131:599–606

    Google Scholar 

  21. Leikauf GD, Driscoll KE, Wey HE (1988) Ozone-induced augmentation of eicosanoid metabolism in epithelial cells from bovine trachea. Am Rev Respir Dis 137:435–442

    Google Scholar 

  22. Matsumoto K, Takata S, Koto H, Inoue H, Aizawa H, Ikeda T, Ito Y (1993) Cultured epithelial cell releases factor(s) other than prostaglandins which inhibit excitatory neuro-effector transmission in canine airway. Am Rev Respir Dis 147:A848

    Google Scholar 

  23. Mattoli S, Mezzetti M, Riva G, Allegra L, Fasoli A (1990) Specific binding of endothelin on human bronchial smooth muscle cells in culture and secretion of endothelin-like material from bronchial epithelial cells. Am J Respir Cell Mol Biol 3:145–151

    Google Scholar 

  24. Munakata M, Mitzner W, Menkes H (1988) Osmotic stimuli induce epithelial-dependent relaxation in the guinea pig trachea. J Appl Physiol 64:466–471

    Google Scholar 

  25. Murlas C (1986) Effects of mucosal removal on guinea-pig airway smooth muscle responsiveness. Clin Sci 70:571–575

    Google Scholar 

  26. O'Byrne PM, Leikauf GD, Aizawa H, Bethel RA, Ueki IF, Holtzman MJ, Nadel JA (1985) Leukotriene B4 induces airway hyperresponsiveness in dogs. J Appl Physiol 59:1941–1946

    Google Scholar 

  27. Raeburn D, Hay DWP, Farmer SG, Feden JS (1986) Epithelium removal increases the reactivity of human isolated tracheal muscle to methacholine and reduces the effect of verapamil. Eur J Pharmacol 123:451–453

    Google Scholar 

  28. Russell JA (1980) Noradrenergic inhibitory innervation of canine airways. J Appl Physiol 48:16–22

    Google Scholar 

  29. Seltzer J, Bigby BG, Stulbarg M, Holtzman MJ, Nadel JA, Ueki IF, Leikauf GD, Goetzl EJ, Boushey HA (1986) O3-induced change in bronchial reactivity to methacholine and airway inflammation in humans. J Appl Physiol 60:1321–1326

    Google Scholar 

  30. Simonsson BG, Jacobs FM, Nadel JA (1967) Role of autonomic nervous system and cough reflex in the increased responsiveness of airways in patients with obstructive airway disease. J Clin Invest 41:1812–1818

    Google Scholar 

  31. Walters EH, O'Byrne PM, Fabbri LM, Graf PD, Holtzman MJ, Nadel JA (1984) Control of neurotransmission by prostaglandins in canine trachealis smooth muscle. J Appl Physiol 57: 129–134

    Google Scholar 

  32. Widdicombe JH, Basbaum CB, Highland E (1981) Ion contents and other properties of isolated cells from dog tracheal epithelium. Am J Physiol 241:C184-C192

    Google Scholar 

  33. Xie Z, Hakoda H, Ito Y (1992) Airway epithelial cells regulate membrane potential, neurotransmission, and muscle tone of the dog airway smooth muscle. J Physiol 449:619–639

    Google Scholar 

  34. Yu X-Y, Hubbard W, Spannhake EW (1992) Inhibition of canine tracheal smooth muscle by mediators from cultured bronchial epithelial cells. Am J Physiol 262:L229-L234

    Google Scholar 

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Aizawa, H., Matsumoto, K., Shigyo, M. et al. Airway epithelial cells modulate cholinergic neurotransmission in dog trachea. Lung 172, 241–249 (1994). https://doi.org/10.1007/BF00164441

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