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. 1992 Aug;106(4):978–985. doi: 10.1111/j.1476-5381.1992.tb14445.x

Adenosine-induced bronchoconstriction of isolated lung and trachea from sensitized guinea-pigs.

J R Thorne 1, K J Broadley 1
PMCID: PMC1907640  PMID: 1393296

Abstract

1. The bronchoconstriction of airway-perfused lungs and contraction of superfused tracheal spirals from guinea-pigs in response to adenosine were examined. 2. In lungs from untreated animals, adenosine had little effect unless the perfusion pressure was raised with carbachol (1.1 microM), when it caused a fall in perfusion pressure. However, if removed from guinea-pigs sensitized with ovalbumin (5 mg and 10 mg i.p. 14 and 12 days before use), adenosine was bronchoconstrictor, exerting bronchodilator effects only at high (1 mg) doses. The constrictor response to adenosine (300 micrograms) was significantly greater than that in lungs from untreated or sham-injected animals. 3. In superfused trachea from untreated animals, adenosine exerted only relaxant responses. In tissues from ovalbumin-sensitized guinea-pigs adenosine produced contractile responses, with relaxation appearing only at high (1 mg) doses. 4. Thus sensitization by antigen challenge revealed a bronchoconstrictor response of isolated airway preparations to adenosine. This is related to the clinical situation where only asthmatic subjects respond to adenosine by bronchoconstriction and suggests that the sensitization may destabilize inflammatory cells for mediator release by adenosine. 5. The response to a second exposure to adenosine was consistently reduced (lungs) or converted to a relaxation (trachea) indicating tachyphylaxis and consistent with a mediator release mechanism. 6. The P1-purinoceptor antagonist, 8-phenyltheophylline (3.9 microM), antagonized the relaxant responses to higher doses of adenosine. However, it did not affect the contractile responses to lower doses of adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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  1. 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]
  2. Advenier C., Devillier P., Matran R., Naline E. Influence of epithelium on the responsiveness of guinea-pig isolated trachea to adenosine. Br J Pharmacol. 1988 Feb;93(2):295–302. doi: 10.1111/j.1476-5381.1988.tb11434.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barnes P. J., Chung K. F., Page C. P. Inflammatory mediators and asthma. Pharmacol Rev. 1988 Mar;40(1):49–84. [PubMed] [Google Scholar]
  4. Brink C., Duncan P. G., Douglas J. S. The response and sensitivity to histamine of respiratory tissues from normal and ovalbumin-sensitized guinea pigs: effects of cyclooxygenase and lipoxygenase inhibition. J Pharmacol Exp Ther. 1981 Jun;217(3):592–601. [PubMed] [Google Scholar]
  5. 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]
  6. CONSTANTINE J. W. THE SPIRALLY CUT TRACHEAL STRIP PREPARATION. J Pharm Pharmacol. 1965 Jun;17:384–385. doi: 10.1111/j.2042-7158.1965.tb07688.x. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Church M. K., Holgate S. T. Adenosine in asthmatic lung. Prog Clin Biol Res. 1988;263:159–166. [PubMed] [Google Scholar]
  9. Church M. K., Hughes P. J., Vardey C. J. Studies on the receptor mediating cyclic AMP-independent enhancement by adenosine of IgE-dependent mediator release from rat mast cells. Br J Pharmacol. 1986 Jan;87(1):233–242. doi: 10.1111/j.1476-5381.1986.tb10176.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Cortijo J., Ortiz J. L., Sanz C., Sarría B., Pascual R., Perpiñ M., Esplugues J., Morcillo E. J. Modification by indomethacin of airway contractile responses in normal and sensitized guinea-pigs. Eur J Pharmacol. 1989 Mar 29;162(3):467–473. doi: 10.1016/0014-2999(89)90337-3. [DOI] [PubMed] [Google Scholar]
  12. Coyle A. J., Urwin S. C., Page C. P., Touvay C., Villain B., Braquet P. The effect of the selective PAF antagonist BN 52021 on PAF- and antigen-induced bronchial hyper-reactivity and eosinophil accumulation. Eur J Pharmacol. 1988 Mar 22;148(1):51–58. doi: 10.1016/0014-2999(88)90453-0. [DOI] [PubMed] [Google Scholar]
  13. Crimi N., Palermo F., Ciccarello C., Oliveri R., Vancheri C., Palermo B., Mistretta A. Effect of theophylline on adenosine-induced bronchoconstriction. Ann Allergy. 1989 Feb;62(2):123–127. [PubMed] [Google Scholar]
  14. Crimi N., Palermo F., Polosa R., Oliveri R., Maccarrone C., Palermo B., Mistretta A. Effect of indomethacin on adenosine-induced bronchoconstriction. J Allergy Clin Immunol. 1989 May;83(5):921–925. doi: 10.1016/0091-6749(89)90106-1. [DOI] [PubMed] [Google Scholar]
  15. Cushley M. J., Holgate S. T. Adenosine-induced bronchoconstriction in asthma: role of mast cell-mediator release. J Allergy Clin Immunol. 1985 Feb;75(2):272–278. doi: 10.1016/0091-6749(85)90057-0. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. 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]
  18. Daffonchio L., Payne A. N., Lees I. W., Whittle B. J. Airway hyperreactivity follows anaphylactic microshock in anaesthetized guinea-pigs. Eur J Pharmacol. 1989 Feb 28;161(2-3):135–142. doi: 10.1016/0014-2999(89)90835-2. [DOI] [PubMed] [Google Scholar]
  19. Daffonchio L., Payne A. N., Lees I. W., Whittle B. J. Immediate anaphylactic bronchoconstriction induces airway hyperreactivity in anaesthetized guinea-pigs. Br J Pharmacol. 1988 Jul;94(3):663–668. doi: 10.1111/j.1476-5381.1988.tb11573.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Darmani N. A., Broadley K. J. Actions and interactions of adenosine, theophylline and enprofylline on the guinea-pig spirally cut trachea. Eur J Pharmacol. 1986 Jun 24;125(3):353–362. doi: 10.1016/0014-2999(86)90791-0. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Farmer S. G., Canning B. J., Wilkins D. E. Adenosine receptor-mediated contraction and relaxation of guinea-pig isolated tracheal smooth muscle: effects of adenosine antagonists. Br J Pharmacol. 1988 Oct;95(2):371–378. doi: 10.1111/j.1476-5381.1988.tb11655.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. Ghai G., Zimmerman M. B., Hopkins M. F. Evidence for A1 and A2 adenosine receptors in guinea pig trachea. Life Sci. 1987 Sep 7;41(10):1215–1224. doi: 10.1016/0024-3205(87)90199-8. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Holgate S. T., Finnerty J. P., Polosa R. Mechanisms of purine-induced bronchoconstriction in asthma. Arch Int Pharmacodyn Ther. 1990 Jan-Feb;303:122–131. [PubMed] [Google Scholar]
  27. Hughes P. J., Holgate S. T., Church M. K. Adenosine inhibits and potentiates IgE-dependent histamine release from human lung mast cells by an A2-purinoceptor mediated mechanism. Biochem Pharmacol. 1984 Dec 1;33(23):3847–3852. doi: 10.1016/0006-2952(84)90050-9. [DOI] [PubMed] [Google Scholar]
  28. Jones T. R., Lefcoe N. M., Hamilton J. T. Pharmacological study of adenosine and related compounds on isolated guinea pig trachea: evidence for more than one type of purine receptor. Can J Physiol Pharmacol. 1980 Nov;58(11):1356–1365. doi: 10.1139/y80-205. [DOI] [PubMed] [Google Scholar]
  29. Kallós P., Kallós L. Experimental asthma in guinea pigs revisited. Int Arch Allergy Appl Immunol. 1984;73(1):77–85. doi: 10.1159/000233441. [DOI] [PubMed] [Google Scholar]
  30. Lohse M. J., Maurer K., Klotz K. N., Schwabe U. Synergistic effects of calcium-mobilizing agents and adenosine on histamine release from rat peritoneal mast cells. Br J Pharmacol. 1989 Dec;98(4):1392–1398. doi: 10.1111/j.1476-5381.1989.tb12689.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Mann J. S., Cushley M. J., Holgate S. T. Adenosine-induced bronchoconstriction in asthma. Role of parasympathetic stimulation and adrenergic inhibition. Am Rev Respir Dis. 1985 Jul;132(1):1–6. doi: 10.1164/arrd.1985.132.1.1. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Mansour S., Daniel E. E. Responsiveness of isolated tracheal smooth muscle from normal and sensitized guinea pigs. Can J Physiol Pharmacol. 1987 Sep;65(9):1942–1950. doi: 10.1139/y87-303. [DOI] [PubMed] [Google Scholar]
  34. Manzini S., Ballati L. 2-Chloroadenosine induction of vagally-mediated and atropine-resistant bronchomotor responses in anaesthetized guinea-pigs. Br J Pharmacol. 1990 Jun;100(2):251–256. doi: 10.1111/j.1476-5381.1990.tb15791.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Marquardt D. L., Parker C. W., Sullivan T. J. Potentiation of mast cell mediator release by adenosine. J Immunol. 1978 Mar;120(3):871–878. [PubMed] [Google Scholar]
  36. Marquardt D. L., Walker L. L. Inhibition of mast cell adenosine responsiveness by chronic exposure to adenosine receptor agonists. Biochem Pharmacol. 1987 Dec 15;36(24):4297–4302. doi: 10.1016/0006-2952(87)90674-5. [DOI] [PubMed] [Google Scholar]
  37. McCaig D. J. Comparison of autonomic responses in the trachea isolated from normal and albumin-sensitive guinea-pigs. Br J Pharmacol. 1987 Dec;92(4):809–816. doi: 10.1111/j.1476-5381.1987.tb11385.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Mitchell H. W., Denborough M. A. Anaphylaxis in guinea-pig peripheral airways in vitro. Eur J Pharmacol. 1979 Feb 15;54(1-2):69–78. doi: 10.1016/0014-2999(79)90409-6. [DOI] [PubMed] [Google Scholar]
  39. Napier F. E., Temple D. M. The relation between effects of adenosine, theophylline and enprofylline on the contractility of sensitized guinea-pig lung strips. J Pharm Pharmacol. 1987 Jun;39(6):432–438. doi: 10.1111/j.2042-7158.1987.tb03415.x. [DOI] [PubMed] [Google Scholar]
  40. Napier F. E., Temple D. M. Theophylline's inhibition of antigen-induced contraction of human parenchymal strips is independent of adenosine antagonism. Eur J Pharmacol. 1987 Oct 13;142(2):253–260. doi: 10.1016/0014-2999(87)90114-2. [DOI] [PubMed] [Google Scholar]
  41. Pauwels R. A., Van der Straeten M. E. An animal model for adenosine-induced bronchoconstriction. Am Rev Respir Dis. 1987 Aug;136(2):374–378. doi: 10.1164/ajrccm/136.2.374. [DOI] [PubMed] [Google Scholar]
  42. Peachell P. T., Columbo M., Kagey-Sobotka A., Lichtenstein L. M., Marone G. Adenosine potentiates mediator release from human lung mast cells. Am Rev Respir Dis. 1988 Nov;138(5):1143–1151. doi: 10.1164/ajrccm/138.5.1143. [DOI] [PubMed] [Google Scholar]
  43. Phillips G. D., Bagga P. K., Djukanovic R., Holgate S. T. The influence of refractoriness to adenosine 5'-monophosphate on allergen-provoked bronchoconstriction in asthma. Am Rev Respir Dis. 1989 Aug;140(2):321–326. doi: 10.1164/ajrccm/140.2.321. [DOI] [PubMed] [Google Scholar]
  44. Phillips G. D., Ng W. H., Church M. K., Holgate S. T. The response of plasma histamine to bronchoprovocation with methacholine, adenosine 5'-monophosphate, and allergen in atopic nonasthmatic subjects. Am Rev Respir Dis. 1990 Jan;141(1):9–13. doi: 10.1164/ajrccm/141.1.9. [DOI] [PubMed] [Google Scholar]
  45. Post M. J., te Biesebeek J. D., Wemer J., van Rooij H. H., Porsius A. J. Adenosine enhances antigen-induced bronchoconstriction and histamine release in rat isolated lungs. Agents Actions. 1990 Apr;30(1-2):30–33. doi: 10.1007/BF01968990. [DOI] [PubMed] [Google Scholar]
  46. Rafferty P., Beasley R., Holgate S. T. The contribution of histamine to immediate bronchoconstriction provoked by inhaled allergen and adenosine 5' monophosphate in atopic asthma. Am Rev Respir Dis. 1987 Aug;136(2):369–373. doi: 10.1164/ajrccm/136.2.369. [DOI] [PubMed] [Google Scholar]
  47. Rankin J. A. The contribution of alveolar macrophages to hyperreactive airway disease. J Allergy Clin Immunol. 1989 Apr;83(4):722–729. doi: 10.1016/0091-6749(89)90005-5. [DOI] [PubMed] [Google Scholar]
  48. Rosengard B. R., Mahalik C., Cochrane D. E. Mast cell secretion: differences between immunologic and non-immunologic stimulation. Agents Actions. 1986 Nov;19(3-4):133–140. doi: 10.1007/BF01966197. [DOI] [PubMed] [Google Scholar]
  49. Saad M. H., Burka J. F. Effects of immunological sensitization on the responses and sensitivity of guinea pig airways to bronchoconstrictors. Modulation by selective inhibition of arachidonic acid metabolism. Can J Physiol Pharmacol. 1983 Aug;61(8):876–887. doi: 10.1139/y83-133. [DOI] [PubMed] [Google Scholar]
  50. Sanjar S., Aoki S., Kristersson A., Smith D., Morley J. Antigen challenge induces pulmonary airway eosinophil accumulation and airway hyperreactivity in sensitized guinea-pigs: the effect of anti-asthma drugs. Br J Pharmacol. 1990 Apr;99(4):679–686. doi: 10.1111/j.1476-5381.1990.tb12989.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Satchell D., Smith R. Adenosine causes contractions in spiral strips and relaxations in transverse strips of guinea-pig trachea: studies on mechanism of action. Eur J Pharmacol. 1984 Jun 1;101(3-4):243–247. doi: 10.1016/0014-2999(84)90163-8. [DOI] [PubMed] [Google Scholar]
  52. Turner N. C., Dollery C. T. Release of arachidonic acid metabolites and histamine from sensitized guinea-pig lung following antigen challenge. Br J Pharmacol. 1988 Apr;93(4):751–758. doi: 10.1111/j.1476-5381.1988.tb11459.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Welton A. F., Simko B. A. Regulatory role of adenosine in antigen-induced histamine release from the lung tissue of actively sensitized guinea pigs. Biochem Pharmacol. 1980 Apr 15;29(8):1085–1092. doi: 10.1016/0006-2952(80)90400-1. [DOI] [PubMed] [Google Scholar]

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