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. 1983 Feb;78(2):[339]-344, 345-351. doi: 10.1111/j.1476-5381.1983.tb09399.x

Distinctive pharmacological profile of a nonadrenergic inhibitory system in bullfrog lung

Hall Downes, Stephen M Taylor
PMCID: PMC2044705  PMID: 6131719

Abstract

1 Bullfrog hemilungs, pretreated with atropine, are markedly relaxed on addition of carbachol. Since the relaxant effect is inhibited by tetrodotoxin or hexamethonium, it is neurally mediated and involves stimulation of nicotinic receptors with release of an unknown inhibitory transmitter.

2 Carbachol-induced relaxation is nonadrenergic since: (a) it considerably exceeds the maximal effects of isoprenaline or the effect of 10-3M adrenaline or noradrenaline; (b) it elicits marked further relaxation in preparations already relaxed by high concentrations of catecholamines; (c) it is not attenuated by low concentrations of propranolol (10-6 and 3 × 10-6M) that competitively antagonize isoprenaline-induced relaxation.

3 Carbachol-induced relaxation has multiple distinguishing characteristics, which serve as a fingerprint for the unknown inhibitory transmitter. These include an exceptionally rapid onset of action, a ceiling effect at 50% of maximal relaxation, and minimal retardation by concentrations of procaine that block or markedly retard relaxant responses to all other agonists.

4 This distinctive pharmacological profile cannot be reproduced by addition of exogenous catecholamines, 5-hydroxytryptamine, adenosine triphosphate (ATP) or adenosine, or by addition of ATP or adenosine following pretreatment with indomethacin. Furthermore, addition of carbachol to preparations previously relaxed with 10-3M concentrations of these agents produced marked, additional relaxation.

5 Maximally effective concentrations of vasoactive intestinal peptide produced a barely detectable relaxant response equivalent to 8% of maximal relaxation. The response was totally prevented by pretreatment with procaine.

6 Carbachol-induced relaxation was not impaired by pretreatment with 10-4M indomethacin.

7 Carbachol-induced relaxation of bullfrog lung therefore involves a postganglionic inhibitory transmitter that in nonadrenergic, non-5-hydroxytryptaminergic, and nonpurinergic, and whose effects are not dependent on prostaglandin synthesis. Although a peptide may function as the inhibitory transmitter, it is not vasoactive intestinal peptide.

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Selected References

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  1. Bortoff A., Muller R. Stimulation of intestinal smooth muscle by atropine, procaine, and tetrodotoxin. Am J Physiol. 1975 Dec;229(6):1609–1613. doi: 10.1152/ajplegacy.1975.229.6.1609. [DOI] [PubMed] [Google Scholar]
  2. Burnstock G., Cocks T., Paddle B., Staszewska-Barczak J. Evidence that prostaglandin is responsible for the 'rebound contraction' following stimulation of non-adrenergic, non-cholinergic ('purinergic') inhibitory nerves. Eur J Pharmacol. 1975 Apr;31(2):360–362. doi: 10.1016/0014-2999(75)90060-6. [DOI] [PubMed] [Google Scholar]
  3. Burnstock G. Evolution of the autonomic innervation of visceral and cardiovascular systems in vertebrates. Pharmacol Rev. 1969 Dec;21(4):247–324. [PubMed] [Google Scholar]
  4. Burnstock G. Purinergic nerves. Pharmacol Rev. 1972 Sep;24(3):509–581. [PubMed] [Google Scholar]
  5. CONWAY E. J. Nature and significance of concentration relations of potassium and sodium ions in skeletal muscle. Physiol Rev. 1957 Jan;37(1):84–132. doi: 10.1152/physrev.1957.37.1.84. [DOI] [PubMed] [Google Scholar]
  6. Campbell G. Autonomic innervation of the lung musculature of a toad (Bufo marinus). Comp Gen Pharmacol. 1971 Sep;2(7):281–286. doi: 10.1016/0010-4035(71)90052-8. [DOI] [PubMed] [Google Scholar]
  7. Campbell G., Duxson M. J. The sympathetic innervation of lung muscle in the toad Bufo marinus: a revision and an explanation. Comp Biochem Physiol C. 1978;60(1):65–73. doi: 10.1016/0306-4492(78)90029-1. [DOI] [PubMed] [Google Scholar]
  8. Campbell G., Haller C. J., Rogers D. C. Fine structural and cytochemical study of the innervation of smooth muscle in an amphibian (Bufo marinus) lung before and after denervation. Cell Tissue Res. 1978 Dec 12;194(3):419–432. doi: 10.1007/BF00236163. [DOI] [PubMed] [Google Scholar]
  9. Chidsey C., Pine M., Favrot L., Smith S., Leonetti G., Morselli P., Zanchetti A. The use of drug concentration measurements in studies of the therapeutic response to propranolol. Postgrad Med J. 1976;52 (Suppl 4):26–32. [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. 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]
  12. Coltart D. J., Meldrum S. J. The effect of racemic propranolol, dextro-propranolol and racemic practolol on the human and canine cardiac transmembrane action potential (beta blockade and the cardiac action potential). Arch Int Pharmacodyn Ther. 1971 Jul;192(1):188–197. [PubMed] [Google Scholar]
  13. Davis L. D., Temte J. V. Effects of propranolol on the transmembrane potentials of ventricular muscle and Purkinje fibers of the dog. Circ Res. 1968 May;22(5):661–677. doi: 10.1161/01.res.22.5.661. [DOI] [PubMed] [Google Scholar]
  14. Dohadwalla A. N., Freedberg A. S., Vaughan Williams E. M. The relevance of beta-receptor blockade to ouabain-induced cardiac arrhythmias. Br J Pharmacol. 1969 Jun;36(2):257–267. doi: 10.1111/j.1476-5381.1969.tb09503.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Donatsch P., Lowe D. A., Richardson B. P., Taylor P. The functional significance of sodium channels in pancreatic beta-cell membranes. J Physiol. 1977 May;267(2):357–376. doi: 10.1113/jphysiol.1977.sp011817. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Downes H., Taylor S. M. A potent, structurally specific stimulant action of procaine in bullfrog lung. Comp Biochem Physiol C. 1982;72(1):39–43. doi: 10.1016/0306-4492(82)90202-7. [DOI] [PubMed] [Google Scholar]
  17. Ferreira S. H., Moncada S., Vane J. R. Indomethacin and aspirin abolish prostaglandin release from the spleen. Nat New Biol. 1971 Jun 23;231(25):237–239. doi: 10.1038/newbio231237a0. [DOI] [PubMed] [Google Scholar]
  18. Furchgott R. F., Zawadzki J. V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373–376. doi: 10.1038/288373a0. [DOI] [PubMed] [Google Scholar]
  19. Holmgren S., Campbell G. Adrenoceptors in the lung of the toad Bufo marinus: regional differences in responses to amines and to sympathetic nerve stimulation. Comp Biochem Physiol C. 1978;60(1):11–18. doi: 10.1016/0306-4492(78)90020-5. [DOI] [PubMed] [Google Scholar]
  20. Howell B. J., Baumgardner F. W., Bondi K., Rahn H. Acid-base balance in cold-blooded vertebrates as a function of body temperature. Am J Physiol. 1970 Feb;218(2):600–606. doi: 10.1152/ajplegacy.1970.218.2.600. [DOI] [PubMed] [Google Scholar]
  21. Kao C. Y. Tetrodotoxin, saxitoxin and their significance in the study of excitation phenomena. Pharmacol Rev. 1966 Jun;18(2):997–1049. [PubMed] [Google Scholar]
  22. Kidokoro Y., Ritchie A. K., Hagiwara S. Effect of tetrodotoxin on adrenaline secretion in the perfused rat adrenal medulla. Nature. 1979 Mar 1;278(5699):63–65. doi: 10.1038/278063a0. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Kosay S., Riker W. K., Guerrero S. Effects of d-tubocurarine on the frog sympathetic ganglion cell and on synaptic function. J Pharmacol Exp Ther. 1972 Feb;180(2):255–264. [PubMed] [Google Scholar]
  25. MEVES H. Die Wirkung von Adrenalin und Adrenalinverwandten auf Gefässe und Muskulatur der Froschlunge. Pflugers Arch. 1953;258(3):200–210. doi: 10.1007/BF00363459. [DOI] [PubMed] [Google Scholar]
  26. MORALES AGUILERA A., VAUGHANWILLIAMS E. M. THE EFFECTS ON CARDIAC MUSCLE OF BETA-RECEPTOR ANTAGONISTS IN RELATION TO THEIR ACTIVITY AS LOCAL ANAESTHETICS. Br J Pharmacol Chemother. 1965 Apr;24:332–338. doi: 10.1111/j.1476-5381.1965.tb01719.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Matsuzaki Y., Hamasaki Y., Said S. I. Vasoactive intestinal peptide: a possible transmitter of nonadrenergic relaxation of guinea pig airways. Science. 1980 Dec 12;210(4475):1252–1253. doi: 10.1126/science.6254154. [DOI] [PubMed] [Google Scholar]
  28. Narahashi T. Mechanism of action of tetrodotoxin and saxitoxin on excitable membranes. Fed Proc. 1972 May-Jun;31(3):1124–1132. [PubMed] [Google Scholar]
  29. Needleman P., Minkes M. S., Douglas J. R., Jr Stimulation of prostaglandin biosynthesis by adenine nucleotides. Profile of prostaglandin release by perfused organs. Circ Res. 1974 Apr;34(4):455–460. doi: 10.1161/01.res.34.4.455. [DOI] [PubMed] [Google Scholar]
  30. Robinson P. M., McLean J. R., Burnstock G. Ultrastructural identification of non-adrenergic inhibitory nerve fibers. J Pharmacol Exp Ther. 1971 Nov;179(2):149–160. [PubMed] [Google Scholar]
  31. Rogers D. C., Haller C. J. Innervation and cytochemistry of the neuroepithelial bodies in the ciliated epithelium of the toad lung (Bufo marinus). Cell Tissue Res. 1978 Dec 29;195(3):395–410. doi: 10.1007/BF00233885. [DOI] [PubMed] [Google Scholar]
  32. Schnizer W., Hoang N. D., Brecht K. Transmitter in der Froschlunge. Pflugers Arch. 1968;304(3):271–283. doi: 10.1007/BF00592130. [DOI] [PubMed] [Google Scholar]
  33. Tarr M., Luckstead E. F., Jurewicz P. A., Haas H. G. Effect of propranolol on the fast inward sodium current in frog atrial muscle. J Pharmacol Exp Ther. 1973 Mar;184(3):599–610. [PubMed] [Google Scholar]
  34. Tripathi H. C., Gambhir S. S. Innervated Straub's heart--a simple method for adrenergic neurone blocking studies. Indian J Med Res. 1978 Jun;67:1051–1054. [PubMed] [Google Scholar]
  35. Wasano K., Yamamoto T. Monoamine-containing granulated cells in the frog lung. Cell Tissue Res. 1978 Oct 17;193(2):201–209. doi: 10.1007/BF00209034. [DOI] [PubMed] [Google Scholar]
  36. Wood M. J., Burnstock G. Innervation of the lungs of the toad (Bufo marinus). I. Physiology and pharmacology. Comp Biochem Physiol. 1967 Sep;22(3):755–766. doi: 10.1016/0010-406x(67)90768-2. [DOI] [PubMed] [Google Scholar]
  37. Wu C. H., Narahashi T. Mechanism of action of propranolol on squid axon membranes. J Pharmacol Exp Ther. 1973 Jan;184(1):155–162. [PubMed] [Google Scholar]
  38. Yeh J. Z., Narahashi T. Mechanism of action of quinidine on squid axon membranes. J Pharmacol Exp Ther. 1976 Jan;196(1):62–70. [PubMed] [Google Scholar]

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