Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1986 Mar;87(3):501–507. doi: 10.1111/j.1476-5381.1986.tb10192.x

The influence of epithelium on the responsiveness of guinea-pig isolated trachea.

M C Holroyde
PMCID: PMC1916580  PMID: 3801763

Abstract

This study was designed to investigate the possibility that tracheal epithelium generates a relaxant factor analogous to the endothelial-derived relaxant factor (EDRF) of vascular tissue. The absence of such a factor following epithelial damage in diseases such as asthma might help to explain the airway hyperreactivity characteristic of such diseases. Removal of epithelium by rubbing enhanced the sensitivity of guinea-pig isolated tracheal chains to 5-hydroxytryptamine, histamine, acetylcholine, adenosine, isoprenaline and also minimally to KCl. Responses to LaCl3 and electrical field stimulation were not affected. Low concentrations of adenosine produced contractions only in tissues denuded of epithelium. In the presence of indomethacin 1.4 microM or dithiothreitol (DTT) 1 microM, dose-response curves to histamine were moved to the left in both control and rubbed tissues, and the maximum response was increased. The difference in sensitivity between tissues with and without epithelium was not affected by indomethacin, but was slightly reduced by DTT. Phenidone (0.1 mM) also increased the maximum responses, but increased the sensitivity only of the tissues with intact epithelium, to the same level as that seen in the tissues denuded of epithelium. Superfusion cascade studies provided no evidence for the generation of a relaxant factor from tracheal epithelium. It is suggested that the supersensitivity produced by removal of the epithelium is not due to the removal of a relaxant factor, but rather to the removal of a permeability barrier, allowing a greater concentration of agonist at the level of the underlying smooth muscle.

Full text

PDF
501

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adcock J. J., Garland L. G. A possible role for lipoxygenase products as regulators of airway smooth muscle reactivity. Br J Pharmacol. 1980 Jun;69(2):167–169. doi: 10.1111/j.1476-5381.1980.tb07886.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Caparrotta L., Cillo F., Fassina G., Gaion R. M. Dual effect of (-)-N6-phenylisopropyl adenosine on guinea-pig trachea. Br J Pharmacol. 1984 Sep;83(1):23–29. doi: 10.1111/j.1476-5381.1984.tb10115.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chand N., Altura B. M. Acetylcholine and bradykinin relax intrapulmonary arteries by acting on endothelial cells: role in lung vascular diseases. Science. 1981 Sep 18;213(4514):1376–1379. doi: 10.1126/science.7268440. [DOI] [PubMed] [Google Scholar]
  4. Cocks T. M., Angus J. A. Endothelium-dependent relaxation of coronary arteries by noradrenaline and serotonin. Nature. 1983 Oct 13;305(5935):627–630. doi: 10.1038/305627a0. [DOI] [PubMed] [Google Scholar]
  5. Cushley M. J., Tattersfield A. E., Holgate S. T. Adenosine-induced bronchoconstriction in asthma. Antagonism by inhaled theophylline. Am Rev Respir Dis. 1984 Mar;129(3):380–384. doi: 10.1164/arrd.1984.129.3.380. [DOI] [PubMed] [Google Scholar]
  6. Cushley M. J., Tattersfield A. E., Holgate S. T. Inhaled adenosine and guanosine on airway resistance in normal and asthmatic subjects. Br J Clin Pharmacol. 1983 Feb;15(2):161–165. doi: 10.1111/j.1365-2125.1983.tb01481.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Denis D., Charleson S., Rackham A., Jones T. R., Ford-Hutchinson A. W., Lord A., Cirino M., Girard Y., Larue M., Rokach J. Synthesis and biological activities of leukotriene F4 and leukotriene F4 sulfone. Prostaglandins. 1982 Dec;24(6):801–814. doi: 10.1016/0090-6980(82)90060-0. [DOI] [PubMed] [Google Scholar]
  8. Flavahan N. A., Aarhus L. L., Rimele T. J., Vanhoutte P. M. Respiratory epithelium inhibits bronchial smooth muscle tone. J Appl Physiol (1985) 1985 Mar;58(3):834–838. doi: 10.1152/jappl.1985.58.3.834. [DOI] [PubMed] [Google Scholar]
  9. Frömter E., Diamond J. Route of passive ion permeation in epithelia. Nat New Biol. 1972 Jan 5;235(53):9–13. doi: 10.1038/newbio235009a0. [DOI] [PubMed] [Google Scholar]
  10. Furchgott R. F., Cherry P. D., Zawadzki J. V., Jothianandan D. Endothelial cells as mediators of vasodilation of arteries. J Cardiovasc Pharmacol. 1984;6 (Suppl 2):S336–S343. doi: 10.1097/00005344-198406002-00008. [DOI] [PubMed] [Google Scholar]
  11. Furchgott R. F. The role of endothelium in the responses of vascular smooth muscle to drugs. Annu Rev Pharmacol Toxicol. 1984;24:175–197. doi: 10.1146/annurev.pa.24.040184.001135. [DOI] [PubMed] [Google Scholar]
  12. Furchgott R. F., Zawadzki J. V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373–376. doi: 10.1038/288373a0. [DOI] [PubMed] [Google Scholar]
  13. Förstermann U., Neufang B. The endothelium-dependent relaxation of rabbit aorta: effects of antioxidants and hydroxylated eicosatetraenoic acids. Br J Pharmacol. 1984 Aug;82(4):765–767. doi: 10.1111/j.1476-5381.1984.tb16472.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Förstermann U., Neufang B. The endothelium-dependent vasodilator effect of acetylcholine: characterization of the endothelial relaxing factor with inhibitors of arachidonic acid metabolism. Eur J Pharmacol. 1984 Aug 3;103(1-2):65–70. doi: 10.1016/0014-2999(84)90190-0. [DOI] [PubMed] [Google Scholar]
  15. Griffith T. M., Edwards D. H., Lewis M. J., Newby A. C., Henderson A. H. The nature of endothelium-derived vascular relaxant factor. Nature. 1984 Apr 12;308(5960):645–647. doi: 10.1038/308645a0. [DOI] [PubMed] [Google Scholar]
  16. Jones T. R., Kannan M. S., Daniel E. E. Ultrastructural study of guinea pig tracheal smooth muscle and its innervation. Can J Physiol Pharmacol. 1980 Aug;58(8):974–983. doi: 10.1139/y80-148. [DOI] [PubMed] [Google Scholar]
  17. Laitinen L. A., Heino M., Laitinen A., Kava T., Haahtela T. Damage of the airway epithelium and bronchial reactivity in patients with asthma. Am Rev Respir Dis. 1985 Apr;131(4):599–606. doi: 10.1164/arrd.1985.131.4.599. [DOI] [PubMed] [Google Scholar]
  18. Machen T. E., Erlij D., Wooding F. B. Permeable junctional complexes. The movement of lanthanum across rabbit gallbladder and intestine. J Cell Biol. 1972 Aug;54(2):302–312. doi: 10.1083/jcb.54.2.302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Wright E. M. Solute and water transport across epithelia. Am Rev Respir Dis. 1983 May;127(5 Pt 2):S3–S8. [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES