GABA and Benzodiazepines
γ-Aminobutyric acid (GABA) is considered one of the most important inhibitory transmitter in the central nervous system (CNS). It is assumed that there are at least two types of GABA receptors: GABAA and GABAB. At the level of the CNS, stimulation of the GABAA receptors decreases parasympathic airway constrictor tone while stimulation of GABAB receptors may exert an inhibitory effect on cough. However, most of the GABA effect on lung functions appear mediated through activation of lung GABAB receptors. Stimulation of these peripheral receptors results in the inhibition of the release of acetylcholine from cholinergic nerves as well as of the release of neuropeptides from the C-fibres of the non-adrenergic non-cholinergic (NANC) systems. These effects suggest that GABAB receptor agonists may usefully inhibit bronchoconstriction, microvascular leakage, mucous secretion and inflammatory effects mediated by these neuromediators of the autonomie nervous system. In addition, GABA inhibits the release of anaphylactic mediators. This latter effect requires the integrity of the epithelium and is blocked by inhibition of the cyclooxygenase. Activation of lung GABAB receptors may also account for the antitussive effect of GABA.
KeywordsAirway Smooth Muscle GABAB Receptor Vagal Nerve Stimulation Diazepam Binding Inhibitor Antitussive Effect
Unable to display preview. Download preview PDF.
- 21.Barnes PH, Barnaniuk JN, Belvisi MG. Neuropeptides in the respiratory tract. Am Rev Respir Dis 191; 144: 1391-1399.Google Scholar
- 22.Boiser DC, Aziz SM, DeGennaro FC, Kreutner W, Egan RW, Siegel MI, Chapman RW. Antitussive effects of GABAB agonists in the cat and guinea-pig. Br J Pharmacol 1993; 110: 491–495.Google Scholar
- 43.Devillier P, Candenas ML, Naline E, Advenier C. Influence of benzodiazepines on the response of the guinea-pig trachea to the contractile action of adenosine. J Pharmacol 1992; 214: 67–74.Google Scholar
- 49.Papadopoulus V, Muklin AG, Costa E, Krueger KE. The peripheral-type benzodiazepine receptor is functionally linked to leydig cell steroidogenesis. J Biol chem 1990; 265: 3772–3779.Google Scholar
- 51.Taupin V, Herbelin A, Descamps-Latscha B, Zavala F. Endogenous anxiogenic peptide, ODN-binding inhibitor, and benzodiazepines enhance the production of interleukin-1 and tumor necrosis factor by human monocytes. Lymphokine Cytokine Res 1991; 1: 7–13.Google Scholar
- 52.Taupin V, Gogusev J, Descamps-Latscha B, Zavala F. Modulation of tumor necrosis factor-α, interleukin-1β, interleukin 6, interleukin 8 and granulocyte/macrophage colony-stimulating factor expression in human monocytes by an endogenous anxiogenic benzodiazepine ligand, triakontetraneuropeptide: evidence for a role of prostaglandins. Mol Pharmacol 1993; 43: 64–69.PubMedGoogle Scholar
- 53.Watson ML, Smith D, Bourne AD, Thompson RC, Westwick J. Cytokines contribute to airway dysfunction in antigen-challenged guinea-pigs: Inhibition of airway hyperreactivity, pulmonary eosinophil accumulation, and tumor necrosis factor generation by pre-treatment with an interleukin-1 receptor antagonist. Am J Respir Cell Mol Biol 1993; 8: 365–369.PubMedGoogle Scholar