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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1988 Feb;93(2):295–302. doi: 10.1111/j.1476-5381.1988.tb11434.x

Influence of epithelium on the responsiveness of guinea-pig isolated trachea to adenosine.

C Advenier 1, P Devillier 1, R Matran 1, E Naline 1
PMCID: PMC1853809  PMID: 3359106

Abstract

1. The influence of epithelium removal on the effects of adenosine on airway contractility was investigated on the guinea-pig isolated trachea. 2. In preparations under resting tone or precontracted with histamine 10(-5) M, removal of the tracheal epithelium resulted in similar shifts to the left of the adenosine concentration-response curves (0.61 +/- 0.18 (P less than 0.05) and 0.80 +/- 0.09 (P less than 0.001) log units; n = 5), corresponding to 4.07 and 6.31 fold potentiations of the relaxant effect of adenosine. 3. In the presence of dipyridamole 10(-5) M the relaxant effects of adenosine were potentiated 85.1 fold on tracheae with epithelium; removal of the epithelium did not produce a significant additional shift to the left of the adenosine concentration-response curves (0.07 +/- 0.03 log units; n = 5; NS). 4. In the absence of dipyridamole, the theophylline-adenosine antagonism was not of the competitive type, irrespective of whether the tracheae were with or without epithelium. 5. In the presence of dipyridamole, this antagonism was likely to be of the competitive type and its characteristics were the same when the epithelium was present or absent. Regression slope and pA2 values were 0.84 and 5.07, respectively, in the presence of epithelium and 0.76 and 4.89, respectively, in its absence. 6. It is suggested that, at least in the guinea-pig isolated trachea model, the airway epithelium seems to be involved only in the uptake and metabolism of adenosine.

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Selected References

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  1. ARUNLAKSHANA O., SCHILD H. O. Some quantitative uses of drug antagonists. Br J Pharmacol Chemother. 1959 Mar;14(1):48–58. doi: 10.1111/j.1476-5381.1959.tb00928.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Advenier C., Bidet D., Floch-Saint-Aubin A., Renier A. Contribution of prostaglandins and thromboxanes to the adenosine and ATP-induced contraction of guinea-pig isolated trachea. Br J Pharmacol. 1982 Sep;77(1):39–44. doi: 10.1111/j.1476-5381.1982.tb09266.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barnes P. J., Cuss F. M., Palmer J. B. The effect of airway epithelium on smooth muscle contractility in bovine trachea. Br J Pharmacol. 1985 Nov;86(3):685–691. doi: 10.1111/j.1476-5381.1985.tb08946.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brown C. M., Collis M. G. Evidence for an A2/Ra adenosine receptor in the guinea-pig trachea. Br J Pharmacol. 1982 Jul;76(3):381–387. doi: 10.1111/j.1476-5381.1982.tb09231.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Christie J., Satchell D. G. Purine receptors in the trachea: is there a receptor for ATP? Br J Pharmacol. 1980 Dec;70(4):512–514. doi: 10.1111/j.1476-5381.1980.tb09768.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Church M. K., Featherstone R. L., Cushley M. J., Mann J. S., Holgate S. T. Relationships between adenosine, cyclic nucleotides, and xanthines in asthma. J Allergy Clin Immunol. 1986 Oct;78(4 Pt 2):670–675. doi: 10.1016/0091-6749(86)90044-8. [DOI] [PubMed] [Google Scholar]
  7. Coleman R. A. Effects of some purine derivatives on the guinea-pig trachea and their interaction with drugs that block adenosine uptake. Br J Pharmacol. 1976 May;57(1):51–57. doi: 10.1111/j.1476-5381.1976.tb07655.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Coleman R. A., Levy G. P. A non-adrenergic inhibitory nervous pathway in guinea-pig trachea. Br J Pharmacol. 1974 Oct;52(2):167–174. doi: 10.1111/j.1476-5381.1974.tb09697.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. 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]
  11. Emmerson J., Mackay D. The zig-zag tracheal strip. J Pharm Pharmacol. 1979 Nov;31(11):798–798. doi: 10.1111/j.2042-7158.1979.tb13666.x. [DOI] [PubMed] [Google Scholar]
  12. Farmer J. B., Farrar D. G. Pharmacological studies with adenine, adenosine and some phosphorylated derivatives on guinea-pig tracheal muscle. J Pharm Pharmacol. 1976 Oct;28(10):748–752. doi: 10.1111/j.2042-7158.1976.tb04040.x. [DOI] [PubMed] [Google Scholar]
  13. Farmer S. G., Fedan J. S., Hay D. W., Raeburn D. The effects of epithelium removal on the sensitivity of guinea-pig isolated trachealis to bronchodilator drugs. Br J Pharmacol. 1986 Oct;89(2):407–414. doi: 10.1111/j.1476-5381.1986.tb10274.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Fredholm B. B., Brodin K., Strandberg K. On the mechanism of relaxation of tracheal muscle by theophylline and other cyclic nucleotide phosphodiesterase inhibitors. Acta Pharmacol Toxicol (Copenh) 1979 Nov;45(5):336–344. doi: 10.1111/j.1600-0773.1979.tb02402.x. [DOI] [PubMed] [Google Scholar]
  16. Frossard N., Muller F. Epithelial modulation of tracheal smooth muscle response to antigenic stimulation. J Appl Physiol (1985) 1986 Oct;61(4):1449–1456. doi: 10.1152/jappl.1986.61.4.1449. [DOI] [PubMed] [Google Scholar]
  17. Goldie R. G., Papadimitriou J. M., Paterson J. W., Rigby P. J., Self H. M., Spina D. Influence of the epithelium on responsiveness of guinea-pig isolated trachea to contractile and relaxant agonists. Br J Pharmacol. 1986 Jan;87(1):5–14. doi: 10.1111/j.1476-5381.1986.tb10150.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hay D. W., Raeburn D., Farmer S. G., Fleming W. W., Fedan J. S. Epithelium modulates the reactivity of ovalbumin-sensitized guinea-pig airway smooth muscle. Life Sci. 1986 Jun 30;38(26):2461–2468. doi: 10.1016/0024-3205(86)90617-x. [DOI] [PubMed] [Google Scholar]
  19. Holroyde M. C. The influence of epithelium on the responsiveness of guinea-pig isolated trachea. Br J Pharmacol. 1986 Mar;87(3):501–507. doi: 10.1111/j.1476-5381.1986.tb10192.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kenakin T. P. The classification of drugs and drug receptors in isolated tissues. Pharmacol Rev. 1984 Sep;36(3):165–222. [PubMed] [Google Scholar]
  21. Kolassa N., Pfleger K., Rummel W. Specificity of adenosine uptake into the heart and inhibition by dipyridamole. Eur J Pharmacol. 1970 Mar;9(3):265–268. doi: 10.1016/0014-2999(70)90221-9. [DOI] [PubMed] [Google Scholar]
  22. Mann J. S., Holgate S. T. Specific antagonism of adenosine-induced bronchoconstriction in asthma by oral theophylline. Br J Clin Pharmacol. 1985 May;19(5):685–692. doi: 10.1111/j.1365-2125.1985.tb02696.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Raeburn D., Hay D. W., Farmer S. G., Fedan J. S. Epithelium removal increases the reactivity of human isolated tracheal muscle to methacholine and reduces the effect of verapamil. Eur J Pharmacol. 1986 Apr 29;123(3):451–453. doi: 10.1016/0014-2999(86)90722-3. [DOI] [PubMed] [Google Scholar]
  24. Tschirhart E., Landry Y. Airway epithelium releases a relaxant factor: demonstration with substance P. Eur J Pharmacol. 1986 Dec 2;132(1):103–104. doi: 10.1016/0014-2999(86)90020-8. [DOI] [PubMed] [Google Scholar]

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