Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi

GABA (γ-Aminobutyric Acid)

  • Vlainic JosipaEmail author
  • Jazvinscak Jembrek Maja
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101632


Historical Background

For a long time, GABA (Fig. 1) was known only as a product of plant and microbial metabolism. It was first synthesized in 1883, and in 1950 it was realized that GABA is present in the mammalian central nervous system. As an inhibitory neurotransmitter, GABA was recognized in 1967 in experiments showing that nerve and muscle cells challenged by GABA undergo ion-mediated changes in conductance similar to those found following activation of inhibitory neurons (for review see Dreifuss et al. 1969). In the following years, dictinct roles, as well as biosynthetic and metabolic pathways of GABA were described, and its place of synthesis determined.
This is a preview of subscription content, log in to check access.


  1. Ben-Ari Y, Gaiarsa J, Tyzio R, Khazipov R. GABA a pioneer transmitter that excites immature neurons and generates primitive oscillations. Physiol Rev. 2007;87:1215–84.  https://doi.org/10.1152/physrev.00017.2006.CrossRefPubMedGoogle Scholar
  2. Benarroch EE. GABAB receptors: structure, functions, and clinical implications. Neurology. 2012;78(8):578–84.  https://doi.org/10.1212/WNL.0b013e318247cd03.CrossRefPubMedGoogle Scholar
  3. Bettler B, Kaupmann K, Mosbacher J, Gassmann M. Molecular structure and physiological functions of GABA(B) receptors. Physiol Rev. 2004;84(3):835–67.  https://doi.org/10.1152/physrev.00036.2003.CrossRefPubMedGoogle Scholar
  4. Dreifuss JJ, Kelly JS, Krnjevic K. Cortical inhibition and γ-aminobutyric acid. Exp Brain Res. 1969;9:137–54.PubMedCrossRefGoogle Scholar
  5. Harada K, Matsuoka H, Fujihara H, Ueta Y, Yanagawa Y, Inoue M. GABA signaling and neuroactive steroids in adrenal medullary chromaffin cells. Front Cell Neurosci. 2016;10(100).  https://doi.org/10.3389/fncel.2016.00100.
  6. Jazvinscak JM, Vlainic J. GABA receptors: pharmacological potential and pitfalls. Curr Pharm Des. 2015;21(34):4943–59.  https://doi.org/10.2174/1381612821666150914121624.CrossRefGoogle Scholar
  7. Jin Z, Mendu SK, Birnir B. GABA is an effective immunomodulatory molecule. Amino Acids. 2013;45(1):87–94.  https://doi.org/10.1007/s00726-011-1193-7.CrossRefPubMedGoogle Scholar
  8. Kaufman DL, Houser CR, Tobin AJ. Two forms of the GABA synthetic enzyme glutamate decarboxylase have distinct intraneuronal distributions and cofactor interactions. J Neurochem. 1991;56:720–3.PubMedCrossRefGoogle Scholar
  9. Knoflach F, Hernandez MC, Bertrand D. GABAA receptor-mediated neurotransmission: not so simple after all. Biochem Pharmacol. 2016;115:10–7.  https://doi.org/10.1016/j.bcp.2016.03.014.CrossRefPubMedGoogle Scholar
  10. Korpi ER, Gründer G, Lüddens H. Drug interactions at GABA(A) receptors. Prog Neurobiol. 2002;67(2):113–59.  https://doi.org/10.1016/S0301-0082(02)00013-8.CrossRefPubMedGoogle Scholar
  11. Löscher W, Frey HH. Transport of GABA at the blood-CSF interface. J Neurochem. 1982;38:1072–9.  https://doi.org/10.1111/j.1471-4159.1982.tb05350.x.CrossRefPubMedGoogle Scholar
  12. McGeer PL, McGeer EG. Amino acid neurotransmitters. In: Siegel G, Agranoff B, Albers RW, Molinoff P, editors. Basic neurochemistry. 4th ed. New York: Raven Press; 1989. p. 311–32.Google Scholar
  13. Modi JP, Prentice H, Wu JY. Regulation of GABA neurotransmission by glutamic acid decarboxylase (GAD). Curr Pharm Des. 2015;21(34):4939–42.  https://doi.org/10.2174/1381612821666150917094343.CrossRefPubMedGoogle Scholar
  14. Olsen RW, DeLorey TM. GABA synthesis, uptake and release. In Basic neurochemistry, 6th ed. Molecular, Cellular and Medical Aspects. Editors: George J Siegel, MD, Editor-in-Chief, Bernard W Agranoff, MD, R Wayne Albers, PhD, Stephen K Fisher, PhD, and Michael D Uhler, PhD. Philadelphia: Lippincott-Raven; 1999.Google Scholar
  15. 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. Pharmacol Rev. 2008;60(3):243–60.  https://doi.org/10.1124/pr.108.00505.
  16. Owens DF, Kriegstein AR. Is there more to GABA than synaptic inhibition? Nat Rev Neurosci. 2002;3(9):715–27.  https://doi.org/10.1038/nrn919.CrossRefPubMedGoogle Scholar
  17. Roberts E, Frankel S. γ-Aminobutyric acid in brain: its formation from glutamic acid. J Biol Chem. 1950;187:55–63.PubMedGoogle Scholar
  18. Roth RJ, Cooper JR, Bloom FE. The biochemical basis of neuropharmacology. Oxford: Oxford University Press; 2003. p. 106.Google Scholar
  19. Schousboe A, Westergaard N, Waagepetersen HS, Larsson OM, Bakken IJ, Sonnewald U. Trafficking between glia and neurons of TCA cycle intermediates and related metabolites. Glia. 1997;21(1):99–105.PubMedCrossRefGoogle Scholar
  20. Sieghart W, Sperk G. Subunit composition, distribution and function of GABA(A) receptor subtypes. Curr Top Med Chem. 2002;2(8):795–816.  https://doi.org/10.2174/1568026023393507.CrossRefPubMedGoogle Scholar
  21. Somogyi R, Wen X, Ma W, Barker JL. Developmental kinetics of GAD family mRNAs parallel neurogenesis in the rat spinal cord. J Neurosci. 1995;15(4):2575–91.PubMedCrossRefGoogle Scholar
  22. Wei J, Wu JY. Post-translational regulation of L-glutamic acid decarboxylase in the brain. Neurochem Res. 2008;33(8):1459–65.  https://doi.org/10.1007/s11064-008-9600-5.PubMedCrossRefGoogle Scholar
  23. Whiting PJ, Bonnert TP, McKernan RM, Farrar S, Le Bourdellès B, Heavens RP, Smith DW, Hewson L, Rigby MR, Sirinathsinghji DJ, Thompson SA, Wafford KA. Molecular and functional diversity of the expanding GABA-A receptor gene family. Ann N Y Acad Sci. 1999;868:645–53.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Department of Molecular MedicineRudjer Boskovic InstituteZagrebCroatia
  2. 2.Department of PsychologyCatholic University of CroatiaZagrebCroatia