Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1993 May;109(1):53–60. doi: 10.1111/j.1476-5381.1993.tb13530.x

Functional characterization of muscarinic receptors in murine airways.

J Garssen 1, H Van Loveren 1, C M Gierveld 1, H Van der Vliet 1, F P Nijkamp 1
PMCID: PMC2175598  PMID: 8495246

Abstract

1. The effects of muscarinic receptor antagonists considered to be selective for M1 receptors (pirenzepine; PZ), M2 receptors (AFDX-116), and for M3 receptors (4-diphenyl acetoxy N-methyl-piperidine (4-DAMP)) were used to investigate the existence of muscarinic receptors subtypes in murine airways. Atropine was used as a nonselective antagonist. The effects of these antagonists were studied upon tracheal contractions induced either by EFS (electric field stimulation) or by application of an exogenous cholinoceptor agonist (arecoline). 2. The muscarinic receptor antagonists tested inhibited arecoline-induced tracheal contractions with the following rank order of potency: 4-DAMP = atropine > pirenzepine = AFDX-116. The rank order of potency of the muscarinic antagonists used in inhibiting EFS-induced tracheal contractions was: 4-DAMP = atropine > PZ > AFDX-116. The pA2 values for these antagonists were similar when compared to the pA2 values determined in guinea-pig and bovine airway smooth muscle. 3. In addition to in vitro studies, the effects of inhalation of the different muscarinic antagonists on lung function parameters in vivo were investigated. Inhalation of 4-DAMP induced a decrease in airway resistance and an increase in lung compliance. In contrast, inhalation of AFDX-116 induced an increase in airway resistance and almost no change in lung compliance. Apart from some minor effects of atropine on airway resistance, atropine, PZ, and pilocarpine failed to induce changes in lung mechanics as determined by in vivo lung function measurements. 4. The results provide evidence for the existence of M3 receptors on murine tracheae that are involved in the contraction of tracheal smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
58

Images in this article

Selected References

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

  1. AMDUR M. O., MEAD J. Mechanics of respiration in unanesthetized guinea pigs. Am J Physiol. 1958 Feb;192(2):364–368. doi: 10.1152/ajplegacy.1958.192.2.364. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Aas P., Fonnum F. Presynaptic inhibition of acetylcholine release. Acta Physiol Scand. 1986 Jul;127(3):335–342. doi: 10.1111/j.1748-1716.1986.tb07913.x. [DOI] [PubMed] [Google Scholar]
  4. Aas P., Maclagan J. Evidence for prejunctional M2 muscarinic receptors in pulmonary cholinergic nerves in the rat. Br J Pharmacol. 1990 Sep;101(1):73–76. doi: 10.1111/j.1476-5381.1990.tb12091.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Barnes P. J. Muscarinic receptor subtypes: implications for lung disease. Thorax. 1989 Mar;44(3):161–167. doi: 10.1136/thx.44.3.161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Barnes P. J. Neural control of human airways in health and disease. Am Rev Respir Dis. 1986 Dec;134(6):1289–1314. doi: 10.1164/arrd.1986.134.5.1289. [DOI] [PubMed] [Google Scholar]
  7. Barnes P. J. The third nervous system in the lung: physiology and clinical perspectives. Thorax. 1984 Aug;39(8):561–567. doi: 10.1136/thx.39.8.561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bartell T. E., Busse W. W. Effect of Bordetella pertussis vaccination in mice and the isolated tracheal response to isoprenaline. Allergy. 1980 Jun;35(4):291–296. doi: 10.1111/j.1398-9995.1980.tb01769.x. [DOI] [PubMed] [Google Scholar]
  9. Beck K. C., Vettermann J., Flavahan N. A., Rehder K. Muscarinic M1 receptors mediate the increase in pulmonary resistance during vagus nerve stimulation in dogs. Am Rev Respir Dis. 1987 Nov;136(5):1135–1139. doi: 10.1164/ajrccm/136.5.1135. [DOI] [PubMed] [Google Scholar]
  10. Blaber L. C., Fryer A. D., Maclagan J. Neuronal muscarinic receptors attenuate vagally-induced contraction of feline bronchial smooth muscle. Br J Pharmacol. 1985 Nov;86(3):723–728. doi: 10.1111/j.1476-5381.1985.tb08951.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Bloom J. W., Baumgartener-Folkerts C., Palmer J. D., Yamamura H. I., Halonen M. A muscarinic receptor subtype modulates vagally stimulated bronchial contraction. J Appl Physiol (1985) 1988 Nov;65(5):2144–2150. doi: 10.1152/jappl.1988.65.5.2144. [DOI] [PubMed] [Google Scholar]
  12. Bloom J. W., Yamamura H. I., Baumgartener C., Halonen M. A muscarinic receptor with high affinity for pirenzepine mediates vagally induced bronchoconstriction. Eur J Pharmacol. 1987 Jan 6;133(1):21–27. doi: 10.1016/0014-2999(87)90201-9. [DOI] [PubMed] [Google Scholar]
  13. Doods H. N., Mathy M. J., Davidesko D., van Charldorp K. J., de Jonge A., van Zwieten P. A. Selectivity of muscarinic antagonists in radioligand and in vivo experiments for the putative M1, M2 and M3 receptors. J Pharmacol Exp Ther. 1987 Jul;242(1):257–262. [PubMed] [Google Scholar]
  14. Eglen R. M., Whiting R. L. Muscarinic receptor subtypes: a critique of the current classification and a proposal for a working nomenclature. J Auton Pharmacol. 1986 Dec;6(4):323–346. doi: 10.1111/j.1474-8673.1986.tb00661.x. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Folkerts G., Henricks P. A., Slootweg P. J., Nijkamp F. P. Endotoxin-induced inflammation and injury of the guinea pig respiratory airways cause bronchial hyporeactivity. Am Rev Respir Dis. 1988 Jun;137(6):1441–1448. doi: 10.1164/ajrccm/137.6.1441. [DOI] [PubMed] [Google Scholar]
  17. Folkerts G., Nijkamp F. P. Haemophilus influenzae induces a potentiated increase in guinea-pig pulmonary resistance to histamine. Eur J Pharmacol. 1985 Dec 10;119(1-2):117–120. doi: 10.1016/0014-2999(85)90329-2. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Garssen J., Van Loveren H., Van Der Vliet H., Nijkamp F. P. An isometric method to study respiratory smooth muscle responses in mice. J Pharmacol Methods. 1990 Nov;24(3):209–217. doi: 10.1016/0160-5402(90)90031-f. [DOI] [PubMed] [Google Scholar]
  20. Gies J. P., Bertrand C., Vanderheyden P., Waeldele F., Dumont P., Pauli G., Landry Y. Characterization of muscarinic receptors in human, guinea pig and rat lung. J Pharmacol Exp Ther. 1989 Jul;250(1):309–315. [PubMed] [Google Scholar]
  21. Hooker C. S., Calkins P. J., Fleisch J. H. On the measurement of vascular and respiratory smooth muscle responses in vitro. Blood Vessels. 1977;14(1):1–11. doi: 10.1159/000158110. [DOI] [PubMed] [Google Scholar]
  22. Ito Y., Yoshitomi T. Autoregulation of acetylcholine release from vagus nerve terminals through activation of muscarinic receptors in the dog trachea. Br J Pharmacol. 1988 Mar;93(3):636–646. doi: 10.1111/j.1476-5381.1988.tb10321.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. MacKay D. How should values of pA2 and affinity constants for pharmacological competitive antagonists be estimated? J Pharm Pharmacol. 1978 May;30(5):312–313. doi: 10.1111/j.2042-7158.1978.tb13237.x. [DOI] [PubMed] [Google Scholar]
  24. Maclagan J., Faulkner D. Effect of pirenzepine and gallamine on cardiac and pulmonary muscarinic receptors in the rabbit. Br J Pharmacol. 1989 Jun;97(2):506–512. doi: 10.1111/j.1476-5381.1989.tb11979.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Madison J. M., Jones C. A., Tom-Moy M., Brown J. K. Affinities of pirenzepine for muscarinic cholinergic receptors in membranes isolated from bovine tracheal mucosa and smooth muscle. Am Rev Respir Dis. 1987 Mar;135(3):719–724. doi: 10.1164/arrd.1987.135.3.719. [DOI] [PubMed] [Google Scholar]
  26. Minette P. A., Barnes P. J. Muscarinic receptor subtypes in lung. Clinical implications. Am Rev Respir Dis. 1990 Mar;141(3 Pt 2):S162–S165. doi: 10.1164/ajrccm/141.3_Pt_2.S162. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Nadel J. A., Barnes P. J. Autonomic regulation of the airways. Annu Rev Med. 1984;35:451–467. doi: 10.1146/annurev.me.35.020184.002315. [DOI] [PubMed] [Google Scholar]
  29. O'Rourke S. T., Flavahan N. A., Vanhoutte P. M. Characterization of muscarinic receptors in canine bronchial smooth muscle. Eur J Pharmacol. 1987 Aug 4;140(1):117–120. doi: 10.1016/0014-2999(87)90643-1. [DOI] [PubMed] [Google Scholar]
  30. Partanen M., Laitinen A., Hervonen A., Toivanen M., Laitinen L. A. Catecholamine- and acetylcholinesterase-containing nerves in human lower respiratory tract. Histochemistry. 1982;76(2):175–188. doi: 10.1007/BF00501920. [DOI] [PubMed] [Google Scholar]
  31. Roffel A. F., Elzinga C. R., Van Amsterdam R. G., De Zeeuw R. A., Zaagsma J. Muscarinic M2 receptors in bovine tracheal smooth muscle: discrepancies between binding and function. Eur J Pharmacol. 1988 Aug 9;153(1):73–82. doi: 10.1016/0014-2999(88)90589-4. [DOI] [PubMed] [Google Scholar]
  32. Sheppard M. N., Kurian S. S., Henzen-Logmans S. C., Michetti F., Cocchia D., Cole P., Rush R. A., Marangos P. J., Bloom S. R., Polak J. M. Neurone-specific enolase and S-100: new markers for delineating the innervation of the respiratory tract in man and other mammals. Thorax. 1983 May;38(5):333–340. doi: 10.1136/thx.38.5.333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Van Oosterhout A. J., Hofman G., Woutersen-Van Nijnanten F. M., Nijkamp F. P. 5-HT1-like receptors mediate potentiation of cholinergic nerve-mediated contraction of isolated mouse trachea. Eur J Pharmacol. 1991 Dec 17;209(3):237–244. doi: 10.1016/0014-2999(91)90175-p. [DOI] [PubMed] [Google Scholar]
  34. van Koppen C. J., Rodrigues de Miranda J. F., Beld A. J., Hermanussen M. W., Lammers J. W., van Ginneken C. A. Characterization of the muscarinic receptor in human tracheal smooth muscle. Naunyn Schmiedebergs Arch Pharmacol. 1985 Nov;331(2-3):247–252. doi: 10.1007/BF00634245. [DOI] [PubMed] [Google Scholar]

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

RESOURCES