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British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1974 Oct;52(2):167–174. doi: 10.1111/j.1476-5381.1974.tb09697.x

A non-adrenergic inhibitory nervous pathway in guinea-pig trachea

RA Coleman, GP Levy
PMCID: PMC1776879  PMID: 4155987

Abstract

1 Electrical stimulation of the guinea-pig isolated tracheal tube causes a biphasic response, initially excitatory and then inhibitory. The excitatory response was abolished by atropine leaving the inhibitory response unaffected.

2 The inhibitory response was greatly reduced but not abolished by propranolol or guanethidine. A residual inhibitory response was still present in tracheas in which sympathetic nerve function had been abolished by pretreatment with syrosingopine or 6-hydroxydopamine. These results show that the inhibitory response is predominantly adrenergic but that a small non-adrenergic component is also present.

3 The non-adrenergic inhibitory response was abolished by lignocaine and tetrodotoxin suggesting that it is nervous in origin.

4 Optimal stimulation parameters for the predominantly adrenergic inhibitory response were a pulse width of 0.7-2 ms, a stimulation period of 7 s and a frequency of 20 Hz. For the non-adrenergic inhibitory response, optimal stimulation parameters were a pulse width of 2 ms, a stimulation period of 12 s and a frequency of 20 Hz.

5 Evidence obtained with pharmacological antagonists, enzyme inhibitors and activators suggested that the transmitter mediating the non-adrenergic inhibitory nervous response is unlikely to be: acetylcholine, histamine, 5-hydroxytryptamine, cyclic 3′,5′-adenosine monophosphate or a prostaglandin.

6 The adenosine uptake blocking drugs dipyridamole, hexobendine and Dilazep potentiated the non-adrenergic inhibitory nervous response and unmasked inhibitory responses to adenosine and adenosine 5′-triphosphate.

7 It is concluded that electrical stimulation of the guinea-pig trachea, in addition to activating cholinergic and adrenergic nervous pathways, may activate a separate and distinct inhibitory nervous pathway. This pathway has some features in common with the non-adrenergic non-cholinergic inhibitory pathways in gastro-intestinal muscle.

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Selected References

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

  1. BUTCHER R. W., SUTHERLAND E. W. Adenosine 3',5'-phosphate in biological materials. I. Purification and properties of cyclic 3',5'-nucleotide phosphodiesterase and use of this enzyme to characterize adenosine 3',5'-phosphate in human urine. J Biol Chem. 1962 Apr;237:1244–1250. [PubMed] [Google Scholar]
  2. Bowman W. C., Stafford A. Effects of dipyridamole on contractions of the cat's nictitating membrane. Eur J Pharmacol. 1968 May;3(2):131–138. doi: 10.1016/0014-2999(68)90064-2. [DOI] [PubMed] [Google Scholar]
  3. Burnstock G. Purinergic nerves. Pharmacol Rev. 1972 Sep;24(3):509–581. [PubMed] [Google Scholar]
  4. Buyniski J. P., Losada M., Bierwagen M. E., Gardier R. W. Cerebral and coronary vascular effects of a symmetrical N,N'-disubstituted hexahydrodiazepine. J Pharmacol Exp Ther. 1972 Jun;181(3):522–528. [PubMed] [Google Scholar]
  5. Buyniski J. P., Rapela C. E. Cerebral and renal vascular smooth muscle responses to adenosine. Am J Physiol. 1969 Dec;217(6):1660–1664. doi: 10.1152/ajplegacy.1969.217.6.1660. [DOI] [PubMed] [Google Scholar]
  6. Coburn R. F., Tomita T. Evidence for nonadrenergic inhibitory nerves in the guinea pig trachealis muscle. Am J Physiol. 1973 May;224(5):1072–1080. doi: 10.1152/ajplegacy.1973.224.5.1072. [DOI] [PubMed] [Google Scholar]
  7. Coleman R. A., Farmer J. B. The inducement of tone and its inhibition in isolated tracheal muscle. J Pharm Pharmacol. 1971 Mar;23(3):220–222. doi: 10.1111/j.2042-7158.1971.tb08648.x. [DOI] [PubMed] [Google Scholar]
  8. Coleman R. A., Levy G. P. Evidence for a non-adrenergic inhibitory nervous pathway in guinea-pig trachea. Br J Pharmacol. 1973 Jun;48(2):360P–361P. [PMC free article] [PubMed] [Google Scholar]
  9. Coleman R. A., Levy G. P. Mechanisms of 6-hydroxydopamine-induced supersensitivity in guinea-pig isolated intact trachea. Br J Pharmacol. 1972 Nov;46(3):528P–529P. [PMC free article] [PubMed] [Google Scholar]
  10. Eyre P. Histamine H2-receptors in the sheep bronchus and cat trachea: the action of burimamide. Br J Pharmacol. 1973 Jun;48(2):321–323. doi: 10.1111/j.1476-5381.1973.tb06920.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. FOSTER R. W. A NOTE ON THE ELECTRICALLY TRANSMURALLY STIMULATED ISOLATED TRACHEA OF THE GUINEA-PIG. J Pharm Pharmacol. 1964 Feb;16:125–128. doi: 10.1111/j.2042-7158.1964.tb07431.x. [DOI] [PubMed] [Google Scholar]
  12. Farmer J. B., Coleman R. A. A new preparation of the isolated intact trachea of the guinea-pig. J Pharm Pharmacol. 1970 Jan;22(1):46–50. doi: 10.1111/j.2042-7158.1970.tb08383.x. [DOI] [PubMed] [Google Scholar]
  13. Farmer J. B., Farrar D. G., Wilson J. The effect of indomethacin on the tracheal smooth muscle of the guinea-pig. Br J Pharmacol. 1972 Nov;46(3):536P–537P. [PMC free article] [PubMed] [Google Scholar]
  14. James G. W. The use of the in vivo trachea preparation of the guinea-pig to asses drug action on lung. J Pharm Pharmacol. 1969 Jun;21(6):379–386. doi: 10.1111/j.2042-7158.1969.tb08271.x. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Kraupp O., Wolner E., Adler-Kastner L., Chirikdjian J. J., Ploszczanski B., Tuisl E. Die Wirkung von Hexobendin auf Sauerstoffverbrauch, Energetik und Substratstoffwechsel des Herzens. Arzneimittelforschung. 1966 Jun;16(6):692–697. [PubMed] [Google Scholar]
  17. MAIN I. H. THE INHIBITORY ACTIONS OF PROSTAGLANDINS ON RESPIRATORY SMOOTH MUSCLE. Br J Pharmacol Chemother. 1964 Jun;22:511–519. doi: 10.1111/j.1476-5381.1964.tb01705.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. MASON D. F. Depolarizing action of neostigmine at an autonomic ganglion. Br J Pharmacol Chemother. 1962 Jun;18:572–587. doi: 10.1111/j.1476-5381.1962.tb01176.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Malmfors T., Sachs C. Degeneration of adrenergic nerves produced by 6-hydroxydopamine. Eur J Pharmacol. 1968 Apr;3(1):89–92. doi: 10.1016/0014-2999(68)90056-3. [DOI] [PubMed] [Google Scholar]
  20. Nott M. W. The possible role of adenosine in the coronary dilator action of some pyrimidopyrimidines and pteridines. Br J Pharmacol. 1970 Jun;39(2):287–295. doi: 10.1111/j.1476-5381.1970.tb12892.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. ORLANS F. B., FINGER K. F., BRODIE B. B. Pharmacological consequences of the selective release of peripheral norepinephrine by syrosingopine (Su 3118). J Pharmacol Exp Ther. 1960 Feb;128:131–139. [PubMed] [Google Scholar]
  22. POSTERNAK T., SUTHERLAND E. W., HENION W. F. Derivatives of cyclic 3',5'-adenosine monophosphate. Biochim Biophys Acta. 1962 Dec 17;65:558–560. doi: 10.1016/0006-3002(62)90475-4. [DOI] [PubMed] [Google Scholar]
  23. Raberger G., Kraupp O. Enhancement of the coronary dilator effect of intravenous and intracoronary administered adenosine by hexobendine in dogs. Eur J Pharmacol. 1971;13(3):312–319. doi: 10.1016/0014-2999(71)90220-2. [DOI] [PubMed] [Google Scholar]
  24. Rikimaru A., Sudoh M. Innervation of the smooth muscle of the guinea-pig trachea. Nihon Heikatsukin Gakkai Zasshi. 1971 Mar;7(1):35–44. doi: 10.1540/jsmr1965.7.35. [DOI] [PubMed] [Google Scholar]
  25. SUTHERLAND E. W., RALL T. W. Fractionation and characterization of a cyclic adenine ribonucleotide formed by tissue particles. J Biol Chem. 1958 Jun;232(2):1077–1091. [PubMed] [Google Scholar]
  26. Sano N., Katsuki S., Kawada M. Enhancement of coronary vasodilator action of adenosne by 1,4-Bis-(3-(3,4,5-trimethoxybenzoyl-oxy)-propyl)-perhydro-1,4-diazepine (Dilazep I.N.N.). Arzneimittelforschung. 1972 Oct;22(10):1655–1658. [PubMed] [Google Scholar]
  27. Stafford A. Potentiation of adenosine and the adenine nucleotides by dipyridamole. Br J Pharmacol Chemother. 1966 Nov;28(2):218–227. doi: 10.1111/j.1476-5381.1966.tb01888.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Trendelenburg U. Mechanisms of supersensitivity and subsensitivity to sympathomimetic amines. Pharmacol Rev. 1966 Mar;18(1):629–640. [PubMed] [Google Scholar]
  29. Vane J. R. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol. 1971 Jun 23;231(25):232–235. doi: 10.1038/newbio231232a0. [DOI] [PubMed] [Google Scholar]
  30. WIDDICOMBE J. G. Regulation of tracheobronchial smooth muscle. Physiol Rev. 1963 Jan;43:1–37. doi: 10.1152/physrev.1963.43.1.1. [DOI] [PubMed] [Google Scholar]
  31. Weston A. H. Nerve-mediated inhibition of mechanical activity in rabbit duodenum and the effects of desensitization to adenosine and several of its derivatives. Br J Pharmacol. 1973 Jun;48(2):302–308. doi: 10.1111/j.1476-5381.1973.tb06916.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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