GABAergic Mechanisms and Modulation of the Anaphylactic Response

  • L. Zilletti
  • M. Ciufi
  • S. Franchi-Micheli
  • G. Gentilini


It is well known than the anaphylactic reaction can be affected by various neurotransmitters. Furthermore, exocytie processes following challenge with antigen can be modulated due to the presence of different neurotransmitter receptors located on the membranes of involved sensitized cells [23, 22]. GABA, through GABAA and GABAB receptors, appears to have a peculiar role as a neuromodulator in the neuro-vegetative system, since it can inhibit or facilitate the release of classical neurotransmitters such as acetylcholine (ACh), norepinephrine (NE) or peptides (for comprehensive and recent reviews see [5, 7]). Thus, the possibility that GABA could interfere with anaphylaxis arose, and this has been the object of our study, performed in in vivo and in vitro models. We have shown that GABAergic drugs can exert a protective effect against allergic bronchospasm in actively sensitized guinea-pigs [20] and in the Schultz-Dale reaction in isolated tissues [33].


Histamine Release Myenteric Plexus GABAB Receptor Gaba Inhibition GABAergic Mechanism 
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  1. 1.
    Belvisi MG, Ichinose M, Barnes PJ (1989) Modulation of non-adrenegic noncholinergic neural bronchoconstriction in guinea-pig airways via GABAB receptors. Br J Pharmacol 97: 1225–1231PubMedGoogle Scholar
  2. 2.
    Bertrand C, Tschirhart E, Landry Y (1989) Nedocromil sodium inhibits IgE- and IgGrelated antigen-induced contraction in guinea-pig trachea. Int Arch Allergy Appl Immunol 88: 439–446PubMedCrossRefGoogle Scholar
  3. 3.
    Brogden RN, Speight TM, Avery GS (1974) Baclofen: a preliminary report of its pharmacological properties and therapeutic efficacy in spasticity. Drugs 8: 1–14PubMedCrossRefGoogle Scholar
  4. 4.
    Dale MN, Zilletti L (1970) The anaphylactic reaction in the longitudinal muscle strips of guinea-pig ileum. Br J Pharmacol 39: 542–550PubMedGoogle Scholar
  5. 5.
    Erdö SL, Bowery NG (1986) GABAergic mechanisms in the mammalian periphery. Raven, New YorkGoogle Scholar
  6. 6.
    Gentilini G, Franchi-Micheli S, Bindi D, Ziletti L (1990) GABA and neuropeptides affect anaphylaxis in guinea-pig airways. Pharmacol Res (to be published)Google Scholar
  7. 7.
    Giotti A, Bartolni A, Failli P, Gentilini G, Malcangio M, Zilletti L (1990)Review of peripheral GABAB effects. In: Bowery NG, Bittiger H, Olpe HR. (eds) GABAB receptors in mammalian funetion. Wiley, Chichester (to be published)Google Scholar
  8. 8.
    Giotti A, Luzzi S, Spagnesi S, Zilletti L (1983) GABAA and GABAB receptor-mediated effects in guinea-pig ileum. Br J Pharmacol 78: 469–478PubMedGoogle Scholar
  9. 9.
    Goldie RG, Fernandes LB, Farmer SG, Hay DW (1990) Airway epithelium-derived inhibitory factor. TIPS 11: 67–69PubMedGoogle Scholar
  10. 10.
    Hay DWP, Farmer SG, Racburn D, Robinson VY, Fleming WW, Fedan J (1986) Airway epithelium modulates the reactivity of guinea-pig respiratory smooth muscle. Eur J Pharmacol 129: 11–18PubMedCrossRefGoogle Scholar
  11. 11.
    Hay DWP, Racburn D, Farmer SG, Fleming WW, Fedan JS (1986) Epithelium modulates the reactivity of ovalbumin-sensitized guinea-pig airway smooth muscle. Life Sei 38: 2461–2468CrossRefGoogle Scholar
  12. 12.
    Herxheimer H (1952) Repeatable “microshocks” of constant strength in guinea-pig anaphylaxis. J Physiol (Lond) 117: 251–255Google Scholar
  13. 13.
    Hill DR, Bowery NB (1981) 3H-baclofen and 3H-GABA bind to bicuculline-insensitive GABAB sites in rat brain. Nature 290: 149–152PubMedCrossRefGoogle Scholar
  14. 14.
    Holroyde MC (1986) The influence of epithelium on the responsiveness of guinea-pig isolated trachea. Br J Pharmacol 87: 501–507PubMedGoogle Scholar
  15. 15.
    Kaplita PV, Waters DH, Triggle DJ (1982) γ-Aminobutyric acid in guinea-pig ileal myenteric plexus. Eur J Pharmacol 79: 43–51PubMedCrossRefGoogle Scholar
  16. 16.
    Kleinrock A, Kilbinger H (1983) γ-Aminobutyric acid and cholinergic transmission in the guinea-pig ileum. Naunyn Schmiedeberg’s Arch Pharmacol 322: 216–220CrossRefGoogle Scholar
  17. 17.
    Kuriyama K, Sze PY (1971) Blood brain barrier to tritiated GABA treated animals. Neuropharmacology 10: 103–108PubMedCrossRefGoogle Scholar
  18. 18.
    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 guinea-pig. Agents Actions 20: 307–309PubMedCrossRefGoogle Scholar
  19. 19.
    Luzzi S, Franchi-Micheli S, Ciuffi M, Rosi E, Zilletti L (1987) Effect of various GABA receptor agonists and antagonists on anaphylactic histamine release in the guinea-pig ileum. Agents Actions 20: 181–184PubMedCrossRefGoogle Scholar
  20. 20.
    Luzzi S, Franchi-Micheli S, Ciuffi M, Zilletti L (1986) Effects of GABA agonists on Herxheimer microshock in guinea-pigs. Agents Actions 18: 245–247PubMedCrossRefGoogle Scholar
  21. 21.
    Luzzi S, Franchi-Micheli S, Spagnesi S, Rosi E, Ciuffi M, Zilletti L (1985) Inhibition of anaphylactic histamine release in vitro by GABA. Agents Actions 16: 160–162PubMedCrossRefGoogle Scholar
  22. 22.
    Masini E, Fantozzi R, Blandina P, Brunelleschi S, Mannaioni PF (1985)The riddle of cholinergic histamine release from mast cells. In: El Iis GP, West GB. (eds) Progress in medicinal chemistry, vol 22. Elsevier, Amsterdam, pp 267–291Google Scholar
  23. 23.
    Masini E, Fantozzi R, Blandina P, Galli A, Bani-Sacchi T, Giotti, ZillettiL, MannanioniPF(1982) Presence of functionally active ß-adrenoceptors in rat mast cells. Correlation between (-) [3H]-dihydroalprenolol binding and inhibition of histamine release. Naunyn Schmiedeberg’s Arch Pharmacol 321: 171–176CrossRefGoogle Scholar
  24. 24.
    Olsen RW, Tobin AJ (1990) Molecular biology of GABAA receptors. FASEB J 4: 1469–1480PubMedGoogle Scholar
  25. 25.
    Ong J, Kerr DIB (1983) GABAA and GABAB receptor-mediated modification of intestinal motility. Eur J Pharmacol 86: 9–17CrossRefGoogle Scholar
  26. 26.
    Oset-Gasque MH, Launay JM, Gonzalez MP (1986)GABAergic mechanisms in blood cells: their possible role. In: Erdö SL, Bowery NG. (eds) GABAergic mechanisms in the mammalian periphery. Raven, New York, pp 305–324Google Scholar
  27. 27.
    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
  28. 28.
    Saria A, Lundberg JM (1985)Neurogenic inflammation. In: Higgs GA, Williams TJ. (eds) Inflammatory mediatros. VCH, Weinheim, pp 77–85Google Scholar
  29. 29.
    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
  30. 30.
    Tschirhart E, Frossard N, Bertrand C, Landry Y (1987) Arachidonic acid metabolites and airway epithelium-dependent relaxant factor. J Pharmacol Exp Ther 243: 310–316PubMedGoogle Scholar
  31. 31.
    Undem BJ, Raible DG, Adkinson NFJr, Adams GKW (1988) Effect of removal of epithelium on antigen-induced smooth muscle contraction and mediator release from guinea-pig isolated trachea. J Pharmacol Exp Ther 244: 659–665PubMedGoogle Scholar
  32. 32.
    Wood JD (1987)Physiology of the enteric nervous system. In: Johnson LR. (ed) Physiology of the gastrointestinal tract, vol 1. Raven, New York, pp 67–109Google Scholar
  33. 33.
    Zilletti L, Luzzi S, Franchi-Micheli S, Rizzotti M, Rosi E, Spagnesi S (1984) Influence of GABA on anaphylactic histamine release in vitro. Agents Actions 14: 478–480PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1992

Authors and Affiliations

  • L. Zilletti
  • M. Ciufi
  • S. Franchi-Micheli
  • G. Gentilini

There are no affiliations available

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