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. 1995 Feb;114(4):881–887. doi: 10.1111/j.1476-5381.1995.tb13286.x

Dysfunction of muscarinic M2 receptors after the early allergic reaction: possible contribution to bronchial hyperresponsiveness in allergic guinea-pigs.

R E ten Berge 1, R E Santing 1, J J Hamstra 1, A F Roffel 1, J Zaagsma 1
PMCID: PMC1510216  PMID: 7773550

Abstract

1. Using a guinea-pig model of allergic asthma, in which the animals display early (0-5 h) and late phase (8-23 h after antigen challenge) bronchoconstrictor reactions, the function of prejunctional inhibitory M2 and postjunctional M3 receptors in isolated tracheal preparations have been investigated. In addition, cardiac M2 receptor function in vitro and bronchial responsiveness to histamine in vivo were evaluated. 2. Sensitivity to inhaled histamine was increased 3.1 fold and 1.6 fold after the early and late allergic reactions (i.e. at 5 h and 23 h after a single ovalbumin challenge), respectively. At 23 h after the last of four allergen challenges, executed on four consecutive days, bronchial hyperresponsiveness to histamine was diminished to 1.3 fold. 3. After the early response, there was no change in cardiac muscarinic M2 receptor function, since in left atria pD2 (-log EC50) and Emax values of pilocarpine and pKB values of AQ-RA 741, a selective M2 receptor antagonist, were not significantly different from controls (unchallenged sensitized animals), and this also applied to methacholine pD2 values for muscarinic M3 receptors in tracheal smooth muscle. 4. Prejunctional inhibitory muscarinic M2 autoreceptors in airway smooth muscle were markedly dysfunctional after the early allergic response, since potentiation of electrically evoked twitch contractions of tracheal preparations by low concentrations of the M2-selective muscarinic receptor antagonists, gallamine, methoctramine, AQ-RA 741 and AF-DX 116, which is the result of M2 receptor blockade, was clearly and significantly diminished compared to controls.(ABSTRACT TRUNCATED AT 250 WORDS)

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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. Andersson P. Antigen-induced bronchial anaphylaxis in actively sensitized guinea-pigs. Pattern of response in relation to immunization regimen. Allergy. 1980 Jan;35(1):65–71. doi: 10.1111/j.1398-9995.1980.tb01718.x. [DOI] [PubMed] [Google Scholar]
  3. Ayala L. E., Ahmed T. Is there loss of protective muscarinic receptor mechanism in asthma? Chest. 1989 Dec;96(6):1285–1291. doi: 10.1378/chest.96.6.1285. [DOI] [PubMed] [Google Scholar]
  4. Barnes P. J., Minette P., Maclagan J. Muscarinic receptor subtypes in airways. Trends Pharmacol Sci. 1988 Nov;9(11):412–416. doi: 10.1016/0165-6147(88)90069-7. [DOI] [PubMed] [Google Scholar]
  5. Barnes P. J. Reactive oxygen species and airway inflammation. Free Radic Biol Med. 1990;9(3):235–243. doi: 10.1016/0891-5849(90)90034-g. [DOI] [PubMed] [Google Scholar]
  6. Bernstein D. I., Ploysongsang Y., Mittman R. J., Piyamahunt A., Bernstein I. L. The relationship between airway responsiveness measured before and after the allergen-induced late asthmatic response. Chest. 1992 Feb;101(2):437–441. doi: 10.1378/chest.101.2.437. [DOI] [PubMed] [Google Scholar]
  7. Cockcroft D. W., Murdock K. Y. Changes in bronchial responsiveness to histamine at intervals after allergen challenge. Thorax. 1987 Apr;42(4):302–308. doi: 10.1136/thx.42.4.302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cockcroft D. W., Ruffin R. E., Dolovich J., Hargreave F. E. Allergen-induced increase in non-allergic bronchial reactivity. Clin Allergy. 1977 Nov;7(6):503–513. doi: 10.1111/j.1365-2222.1977.tb01481.x. [DOI] [PubMed] [Google Scholar]
  9. Cockcroft D. W., Ruffin R. E., Frith P. A., Cartier A., Juniper E. F., Dolovich J., Hargreave F. E. Determinants of allergen-induced asthma: dose of allergen, circulating IgE antibody concentration, and bronchial responsiveness to inhaled histamine. Am Rev Respir Dis. 1979 Nov;120(5):1053–1058. doi: 10.1164/arrd.1979.120.5.1053. [DOI] [PubMed] [Google Scholar]
  10. Daffonchio L., Lees I. W., Payne A. N., Whittle B. J. Pharmacological modulation of bronchial anaphylaxis induced by aerosol challenge in anaesthetized guinea-pigs. Br J Pharmacol. 1987 Jul;91(3):701–708. doi: 10.1111/j.1476-5381.1987.tb11265.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Durham S. R., Craddock C. F., Cookson W. O., Benson M. K. Increases in airway responsiveness to histamine precede allergen-induced late asthmatic responses. J Allergy Clin Immunol. 1988 Nov;82(5 Pt 1):764–770. doi: 10.1016/0091-6749(88)90077-2. [DOI] [PubMed] [Google Scholar]
  12. Faulkner D., Fryer A. D., Maclagan J. Postganglionic muscarinic inhibitory receptors in pulmonary parasympathetic nerves in the guinea-pig. Br J Pharmacol. 1986 May;88(1):181–187. doi: 10.1111/j.1476-5381.1986.tb09485.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fryer A. D., Jacoby D. B. Effect of inflammatory cell mediators on M2 muscarinic receptors in the lungs. Life Sci. 1993;52(5-6):529–536. doi: 10.1016/0024-3205(93)90311-p. [DOI] [PubMed] [Google Scholar]
  14. Fryer A. D., Jacoby D. B. Parainfluenza virus infection damages inhibitory M2 muscarinic receptors on pulmonary parasympathetic nerves in the guinea-pig. Br J Pharmacol. 1991 Jan;102(1):267–271. doi: 10.1111/j.1476-5381.1991.tb12164.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Fryer A. D., Maclagan J. Muscarinic inhibitory receptors in pulmonary parasympathetic nerves in the guinea-pig. Br J Pharmacol. 1984 Dec;83(4):973–978. doi: 10.1111/j.1476-5381.1984.tb16539.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Fryer A. D., Wills-Karp M. Dysfunction of M2-muscarinic receptors in pulmonary parasympathetic nerves after antigen challenge. J Appl Physiol (1985) 1991 Dec;71(6):2255–2261. doi: 10.1152/jappl.1991.71.6.2255. [DOI] [PubMed] [Google Scholar]
  17. Holtzman M. J., Sheller J. R., Dimeo M., Nadel J. A., Boushey H. A. Effect of ganglionic blockade on bronchial reactivity in atopic subjects. Am Rev Respir Dis. 1980 Jul;122(1):17–25. doi: 10.1164/arrd.1980.122.1.17. [DOI] [PubMed] [Google Scholar]
  18. Hulbert W. C., McLean T., Wiggs B., Paré P. D., Hogg J. C. Histamine dose-response curves in guinea pigs. J Appl Physiol (1985) 1985 Feb;58(2):625–634. doi: 10.1152/jappl.1985.58.2.625. [DOI] [PubMed] [Google Scholar]
  19. Larsen G. L., Fame T. M., Renz H., Loader J. E., Graves J., Hill M., Gelfand E. W. Increased acetylcholine release in tracheas from allergen-exposed IgE-immune mice. Am J Physiol. 1994 Mar;266(3 Pt 1):L263–L270. doi: 10.1152/ajplung.1994.266.3.L263. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Minette P. A., Barnes P. J. Prejunctional inhibitory muscarinic receptors on cholinergic nerves in human and guinea pig airways. J Appl Physiol (1985) 1988 Jun;64(6):2532–2537. doi: 10.1152/jappl.1988.64.6.2532. [DOI] [PubMed] [Google Scholar]
  22. Minette P. A., Lammers J. W., Dixon C. M., McCusker M. T., Barnes P. J. A muscarinic agonist inhibits reflex bronchoconstriction in normal but not in asthmatic subjects. J Appl Physiol (1985) 1989 Dec;67(6):2461–2465. doi: 10.1152/jappl.1989.67.6.2461. [DOI] [PubMed] [Google Scholar]
  23. Okayama M., Shen T., Midorikawa J., Lin J. T., Inoue H., Takishima T., Shirato K. Effect of pilocarpine on propranolol-induced bronchoconstriction in asthma. Am J Respir Crit Care Med. 1994 Jan;149(1):76–80. doi: 10.1164/ajrccm.149.1.8111602. [DOI] [PubMed] [Google Scholar]
  24. Santing R. E., Meurs H., van der Mark T. W., Remie R., Oosterom W. C., Brouwer F., Zaagsma J. A novel method to assess airway function parameters in chronically instrumented, unrestrained guinea-pigs. Pulm Pharmacol. 1992 Dec;5(4):265–272. doi: 10.1016/0952-0600(92)90069-s. [DOI] [PubMed] [Google Scholar]
  25. Santing R. E., Olymulder C. G., Zaagsma J., Meurs H. Relationships among allergen-induced early and late phase airway obstructions, bronchial hyperreactivity, and inflammation in conscious, unrestrained guinea pigs. J Allergy Clin Immunol. 1994 Jun;93(6):1021–1030. doi: 10.1016/s0091-6749(94)70051-6. [DOI] [PubMed] [Google Scholar]
  26. Santing R. E., Schraa E. O., Wachters A., Olymulder C. G., Zaagsma J., Meurs H. Role of histamine in allergen-induced asthmatic reactions, bronchial hyperreactivity and inflammation in unrestrained guinea pigs. Eur J Pharmacol. 1994 Mar 11;254(1-2):49–57. doi: 10.1016/0014-2999(94)90369-7. [DOI] [PubMed] [Google Scholar]
  27. Schultheis A. H., Bassett D. J., Fryer A. D. Ozone-induced airway hyperresponsiveness and loss of neuronal M2 muscarinic receptor function. J Appl Physiol (1985) 1994 Mar;76(3):1088–1097. doi: 10.1152/jappl.1994.76.3.1088. [DOI] [PubMed] [Google Scholar]
  28. Ten Berge R. E., Roffel A. F., Zaagsma J. The interaction of selective and non-selective antagonists with pre- and postjunctional muscarinic receptor subtypes in the guinea pig trachea. Eur J Pharmacol. 1993 Mar 23;233(2-3):279–284. doi: 10.1016/0014-2999(93)90062-m. [DOI] [PubMed] [Google Scholar]
  29. Vidruk E. H., Hahn H. L., Nadel J. A., Sampson S. R. Mechanisms by which histamine stimulates rapidly adapting receptors in dog lungs. J Appl Physiol Respir Environ Exerc Physiol. 1977 Sep;43(3):397–402. doi: 10.1152/jappl.1977.43.3.397. [DOI] [PubMed] [Google Scholar]
  30. Wanner A., Abraham W. M., Douglas J. S., Drazen J. M., Richerson H. B., Ram J. S. NHLBI Workshop Summary. Models of airway hyperresponsiveness. Am Rev Respir Dis. 1990 Jan;141(1):253–257. doi: 10.1164/ajrccm/141.1.253. [DOI] [PubMed] [Google Scholar]
  31. Yang Z. J., Biggs D. F. Muscarinic-receptor functioning in tracheas from normal and ovalbumin-sensitive guinea pigs. Can J Physiol Pharmacol. 1991 Jun;69(6):871–876. doi: 10.1139/y91-132. [DOI] [PubMed] [Google Scholar]
  32. van Amsterdam R. G., Brouwer F., Zaagsma J. Analysis of the beta-adrenoceptor mediated inhibition of IgG1 and IgE dependent guinea-pig anaphylactic tracheal smooth muscle contraction. Agents Actions. 1989 Jan;26(1-2):48–51. doi: 10.1007/BF02126559. [DOI] [PubMed] [Google Scholar]

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