Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

GABAA Receptor

  • Mikko Uusi-Oukari
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_430

Synonyms

Historical Background

γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian brain, where it was first discovered in 1950. It is a small zwitterionic γ-amino acid with molecular weight of 103 g/mol (Fig. 1). Such a hydrophilic molecule cannot cross the blood brain barrier. It is produced in the brain by decarboxylation of L-glutamate by the enzyme glutamic acid decarboxylase (GAD). GABA was recognized as an inhibitory transmitter in 1967. It interacts with two types of receptors: ionotropic GABA A receptors (GABA ARs) that are fast-acting ligand-gated chloride channels, and metabotropic GABA B receptors that are coupled indirectly via G Proteins to either Ca 2+ or K + channels to produce slow and prolonged inhibitory responses. The first GABA AR subunits were cloned in 1987. Since then, molecular biological, electrophysiological, and pharmacological studies have revealed the highly...
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References

  1. Belelli D, Harrison NL, Maguire J, Macdonald RL, Walker MC, Cope DW. Extrasynaptic GABAA receptors: form, pharmacology, and function. J Neurosci. 2009;29:12757–63.PubMedPubMedCentralCrossRefGoogle Scholar
  2. Ben-Ari Y, Gaiarsa JL, Tyzio R, Khazipov R. GABA: a pioneer transmitter that excites immature neurons and generates primitive oscillations. Physiol Rev. 2007;87:1215–84.PubMedCrossRefGoogle Scholar
  3. Froestl W. An historical perspective on GABAergic drugs. Future Med Chem. 2011;3:163–75.PubMedCrossRefGoogle Scholar
  4. Gault LM, Siegel RE. NMDA receptor stimulation selectively initiates GABA(A) receptor delta subunit mRNA expression in cultured rat cerebellar granule neurons. J Neurochem. 1998;70:1907–15.PubMedCrossRefGoogle Scholar
  5. Hu Y, Lund IV, Gravielle MC, Farb DH, Brooks-Kayal AR, Russek SJ. Surface expression of GABAA receptors is transcriptionally controlled by the interplay of cAMP-response element-binding protein and its binding partner inducible cAMP early repressor. J Biol Chem. 2008;283:9328–40.PubMedPubMedCentralCrossRefGoogle Scholar
  6. Jovanovic JN, Thomson AM. Development of cortical GABAergic innervation. Front Cell Neurosci. 2011;5:14.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Laurie DJ, Seeburg PH, Wisden W. The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. II. Olfactory bulb and cerebellum. J Neurosci. 1992a;12:1063–76.PubMedCrossRefGoogle Scholar
  8. Laurie DJ, Wisden W, Seeburg PH. The distribution of thirteen GABAA receptor subunit mRNAs in the rat brain. III. Embryonic and postnatal development. J Neurosci. 1992b;12:4151–72.PubMedCrossRefGoogle Scholar
  9. Lund IV, Hu Y, Raol YH, Benham RS, Faris R, Russek SJ, Brooks-Kayal AR. BDNF selectively regulates GABAA receptor transcription by activation of the JAK/STAT pathway. Sci Signal. 2008;1:ra9.PubMedPubMedCentralCrossRefGoogle Scholar
  10. Luscher B, Fuchs T, Kilpatrick CL. GABAA receptor trafficking-mediated plasticity of inhibitory synapses. Neuron. 2011;70:385–409.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Lyons HR, Land MB, Gibbs TT, Farb DH. Distinct signal transduction pathways for GABA-induced GABA(A) receptor down-regulation and uncoupling in neuronal culture: a role for voltage-gated calcium channels. J Neurochem. 2001;78:1114–26.PubMedCrossRefGoogle Scholar
  12. Mele M, Leal G, Duarte CB. Role of GABAAR trafficking in the plasticity of inhibitory synapses. J Neurochem. 2016.  https://doi.org/10.1111/jnc.13742.CrossRefPubMedGoogle Scholar
  13. Oh WC, Lutzu S, Castillo PE, Kwon HB. De novo synaptogenesis induced by GABA in the developing mouse cortex. Science. 2016;6303:1037–40.CrossRefGoogle Scholar
  14. Olsen RW, Sieghart W. International Union of Pharmacology. LXX. Subtypes of gamma-aminobutyric acid(A) receptors: classification on the basis of subunit composition, pharmacology, and function. Update. Pharmacol Rev. 2008;60:243–60.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Uusi-Oukari M, Korpi ER. Regulation of GABA(A) receptor subunit expression by pharmacological agents. Pharmacol Rev. 2010;62:97–135.PubMedCrossRefGoogle Scholar
  16. Vithlani M, Terunuma M, Moss SJ. The dynamic modulation of GABAA receptor trafficking and its role in regulating the plasticity of inhibitory synapses. Physiol Rev. 2011;91:1009–22.PubMedPubMedCentralCrossRefGoogle Scholar
  17. Whiting PJ. GABA-A receptor subtypes in the brain: a paradigm for CNS drug discovery? Drug Discov Today. 2003;8:445–50.PubMedCrossRefGoogle Scholar
  18. Wisden W, Laurie DJ, Monyer H, Seeburg PH. The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. I. Telencephalon, diencephalon, mesencephalon. J Neurosci. 1992;12:1040–62.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Pharmacology, Drug Development and Therapeutics, Institute of BiomedicineUniversity of TurkuTurkuFinland