GABA‐mediated inhibition of the anaphylactic response in the guinea‐pig trachea

Abstract

In sensitized guinea‐pigs, the effects of γ‐aminobutyric acid (GABA) and GABAmimetic drugs have been investigated on tracheal segments contracted by cumulative application of an allergen (ovoalbumin, OA) and on serosal mast cells. The same drugs have also been tested on activation of alveolar macrophages isolated from unsensitized guinea‐pigs. Superfusion with GABA (1–1000 μM) reduced the contraction intensity of tracheal strips. The effect of GABA (100 μM) was not affected by the carrier blockers, nipecotic acid and β‐alanine (300 μM each). It was mimicked by the GABAB agonist (−)−baclofen (100 μM) but not 3‐aminopropanephosphinic acid (100 μM, 3‐APA). The GABAA agonist, isoguvacine (100 μM) did not exert any effect. GABA (10 μM)‐induced inhibition of tracheal contractions was reduced by the GABAB antagonist, 2‐hydroxysaclofen (100 μM, 2‐HS), but not by the GABAA antagonist, bicuculline (30 μM). The reduction in contraction intensity induced by GABA (100 μM) was prevented by a 40 min preincubation of tracheal strips with capsaicin (10 μM), but not tetrodotoxin (TTX, 0.3 μM). The effect of GABA (1000 μM) was absent after preincubation with indomethacin (2.8 μM) but unmodified when nordihydroguaiaretic acid (NDGA, 3.3 μM) was used. Finally, removal of the epithelium prevented the GABA effect. Anaphylactic histamine release from serosal mast cells isolated from sensitized animals was not affected either by GABA (10–1000 μM) or the selective receptor agonists (−)−baclofen (0.1–1000 μM) and isoguvacine (10–1000 μM). The release of platelet‐activating factor (PAF) from alveolar macrophages stimulated by formyl‐Met‐Leu‐Phe (FMLP; 1 μM) was modified neither by GABA (100 μM) nor by (−)−baclofen (100 μM). In conclusion, these data show that GABA can inhibit allergic phenomena in the guinea‐pig airways through activation of GABAB receptors. An involvement of neuropeptidergic sensory structures is suggested but a role for epithelial cells and arachidonate metabolites is not definitely proved.

Antitussive effects of the peripherally restricted GABAB receptor agonist lesogaberan in guinea pigs: Comparison to baclofen and other GABAB receptor-selective agonists

“…Acid evoked cough may be mast cell dependent, and mast cell activation may trigger or at least modulate subsequently evoked cough [51,52]. GABA B receptor agonists can attenuate allergen-induced inflammation, perhaps through effects on mast cell activation [53,54]. GABA B receptors on non-neural airway cells has also been documented, including airway smooth muscle and epithelium [55,56], and we have described a transduction pathway dependent upon activation of chemosensory epithelial cells [57].…”

Radiation protection following nuclear power accidents: a survey of putative mechanisms involved in the radioprotective actions of taurine during and after radiation exposure.

“…inhibition of release of substance P from capsaicin-sensitive neurones in the rat trachea (578) and of acetylcholine secretion from cholinergic nerves in the lung and in the colon (576–578). GABA itself has been shown to inhibit the anaphylactic response in guinea-pig trachea (579). It has been found that there are different subtypes of GABA B receptors in the central nervous system which differ in their sensitivity to taurine as an agonist (while all of them, of course, are sensitive to GABA).…”

Effect Of Experimental Diabetes On Gaba‐Mediated Inhibition Of Neurally Induced Contractions In Rat Isolated Trachea

“…1 The parasympathetic nervous system plays a dominant role in the control and regulation of the respiratory system in humans and in animals. 4,[8][9][10][11][12][13] In the airways, GABA has been implicated in the regulation of tracheal smooth muscle tone through both central and peripheral mechanisms. 2 It is known that GABA is a major inhibitory neurotransmitter and neuromodulator of the central and peripheral nervous systems.…”