GABAergic Mechanisms in the Pulmonary System

  • R. W. Chapman
  • J. A. Hey
  • D. C. Bolser
  • C. A. Rizzo
  • R. W. Egan
  • W. Kreutner
Conference paper


GABA is a well known inhibitory neurotransmitter in the central nervous system (CNS) that has recently been detected in a variety of peripheral organs [25]. In the lung, GABA has also been implicated as an inhibitory neurotransmitter. It attenuates the contractile response of the isolated guinea-pig trachea to electrical field Stimulation [8, 22, 23], inhibits the release of acetylcholine from guinea-pig lungs [23], and reduces bronchoconstrictor responses to nonadrenergic, noncholinergic Stimulation in guinea-pig airways [2]. However, there is no consensus as to whether the effects of GABA are mediated through an interaction with the well characterized GABAA receptor or rather with the GABAB receptor whose function is not as well understood [4]. In this chapter, we will review the status of GABA as an inhibitory neurotransmitter in the pulmonary system and provide support for GABAB receptors as functionally important for the inhibitory effects of GABA.


GABAs Receptor Airway Smooth Muscle GABAB Receptor Electrical Field Stimulation Vagal Nerve Stimulation 
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  1. 1.
    Barnes PJ (1986) Neural control of human airways in health and disease. Am Rev Respir Dis 134: 1289–1314PubMedGoogle Scholar
  2. 2.
    Belvisi MG, Ichinose M, Barnes PJ (1989) Modulation of non-adrenergic, noncholinergic neural bronchoconstriction in guinea-pig airways via GABAB receptors. Br J Pharmacol 97: 1225–1231PubMedGoogle Scholar
  3. 3.
    Bergren DR, Gustafson JM, Myers DL (1984) Effect of Prostaglandin F on pulmonary rapidly adapting receptors in the guinea-pig. Prostaglandins 3: 391–405CrossRefGoogle Scholar
  4. 4.
    Bowery NG (1989) GABAB receptors and their significance in mammalian pharmacology. Trends Pharmacol Sei 10: 401–407CrossRefGoogle Scholar
  5. 5.
    Bowery NG, Doble A, Hill DR, Hudson AL, Shaw JS, Turnbull MJ, Warrington R (1981) Bicuculline-insensitive GABA receptors on peripheral autonomic nerve terminals. Eur J Pharmacol 71: 53–70PubMedCrossRefGoogle Scholar
  6. 6.
    Chapman RW, Danko G (1989) Inhibitory effect of GABAB receptors on vagally mediated bronchoconstriction in guinea-pigs. FASEB J 3: A440Google Scholar
  7. 7.
    Chapman RW, Danko G (1990) Role of cholinergic, vagal reflexes on the bronchoconstrictor responses to histamine during carbon dioxide inhalation in conscious guinea-pigs. Pharmacol Res 22: 133–141PubMedCrossRefGoogle Scholar
  8. 8.
    Chapman RW, Danko G, Rizzo C, Egan RW, Mauser PJ, Kreutner W (1990) Prejunctional GABAB inhibition of cholinergic, neurally mediated airway contractions in guinea-pigs (to be published)Google Scholar
  9. 9.
    Chapman RW, Kreutner W, del Prado M, Hey JA (1990) Role of GABAB receptors on cholinergic and peptidergic bronchoconstriction in guinea-pigs. International Symposium on Peripheral GABAergic Mechanisms, 19-21 July 1990Google Scholar
  10. 10.
    Del Rio RM, Caballero AL (1980) Presence of γ-aminobutyric acid in rat ovary. J Neurochem 34: 1584–1586CrossRefGoogle Scholar
  11. 11.
    Drazen JM, Austen KF (1975) Atropine modification of pulmonary effects of chemical mediators in the guinea-pig. J Appl Physiol 38: 834–838PubMedGoogle Scholar
  12. 12.
    Gerber JC, Hare TA (1979) Gamma-aminobutyric acid in peripheral tissue, with emphasis on the endocrine pancreas. Diabetes 28: 1073–1076PubMedCrossRefGoogle Scholar
  13. 13.
    Hey JA, del Prado M, Chapman RW (1990) Evidence for a novel medullary bronchomotor pathway that modulates bronchial smooth muscle tone in guinea-pigs. Pulmon Pharmacol 3: 53–54CrossRefGoogle Scholar
  14. 14.
    Hills JM, Dingsdale RA Parsons ME, Dolle RE, Howson W (1989) 3-Aminopropylphosphinic acid, a potent, selective GABAB receptor agonist in the guinea-pig ileum and rat anococcygeus muscle. Br J Pharmacol 97: 1292–1296PubMedGoogle Scholar
  15. 15.
    Luzzi S, Franchi-Micheli S, Ciuffi M, Zilletti L (1986) Effects of GABA agonists on Herxheimer microshock in guinea-pigs. Agents Actions 1/2: 245–247CrossRefGoogle Scholar
  16. 16.
    Luzzi S, Franchi-Micheli S, Folco G, Rossoni G, Ciuffi M, Zilletti L (1987) Effect of baclofen on different models of bronchial hyperreactivity in the guiriea-pig. Agents Actions 3/4: 307–309CrossRefGoogle Scholar
  17. 17.
    Mak JC, Barnes PJ (1989) Peripheral type benzodiazepine receptors in human and guinea-pig lung: characterization and autoradiographic mapping. J Pharmacol Exp Ther 252: 880–885Google Scholar
  18. 18.
    Mauser PJ, Edelman NH, Chapman RW (1988) Central nervous system control of airway tone in guinea-pigs. J Appl Physiol 65: 2024–2029PubMedGoogle Scholar
  19. 19.
    Mauser PJ (1989) Inhibitory effect of GABA on the bronchoconstriction due to intracerebroventricular histamine in guinea-pigs. Am Rev Respir Dis 139: A107Google Scholar
  20. 20.
    Michoud M-C, Fraser RS, Pare PD, Hogg JC (1976) Effect of indomethacin and atropine in experimental asthma in conscious guinea-pigs. J Appl Physiol 40: 889–894PubMedGoogle Scholar
  21. 21.
    Ray NJ, Jones AJ, Keen P (1989) Evidence that GABAB receptors can modulate release of substance P from capsaicin-sensitive neurons in rat trachea. Br J Pharmacol 97: 562PGoogle Scholar
  22. 22.
    Rizzo C, Kreutner W (1989) Prejunctional GABAB inhibition of electrically stimulated contraction in isolated guinea-pig trachea. FASEB J 3: A440Google Scholar
  23. 23.
    Shirakawa J, Taniyama K, Tanaka C (1987) γ-Aminobutyric acid-induced modulation of acetylcholine release from the guinea-pig lung. J Pharmacol Exp Ther 243: 364–369PubMedGoogle Scholar
  24. 24.
    Tamaoki J, Graf PD, Nadel JA (1987) Effect of γ-Aminobutyric acid on neuronally mediated contraction of guinea-pig trachealis smooth muscle. J Pharmacol Exp Ther 243: 86–90PubMedGoogle Scholar
  25. 25.
    Tanaka C (1985) γ-Aminobutyric acid in peripheral tissues. Life Sei 37: 2221–2235CrossRefGoogle Scholar
  26. 26.
    Tsuji M, Nakajima T (1978) Studies on the formation of γ-aminobutyric acid from putrescine in rat organs and purification of its synthetic enzyme from rat intestine. J Biochem 83: 1407–1412PubMedGoogle Scholar
  27. 27.
    Verma A, Snyder SH (1989) Peripheral type benzodiazepine receptors. Ann Rev Pharmacol Toxicol 29: 307–322CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1992

Authors and Affiliations

  • R. W. Chapman
  • J. A. Hey
  • D. C. Bolser
  • C. A. Rizzo
  • R. W. Egan
  • W. Kreutner

There are no affiliations available

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