 | |
 | |
| Names | |
|---|---|
| Pronunciation | /ˈɡæmə əˈmiːnoʊbjuːˈtɪrɪk ˈæsɪd/, /ˈɡæbə/ (GABA) |
| Preferred IUPAC name
4-Aminobutanoic acid | |
Other names
| |
| Identifiers | |
3D model (JSmol)
|
|
| 906818 | |
| ChEBI | |
| ChEMBL | |
| ChemSpider | |
| DrugBank | |
| ECHA InfoCard | 100.000.235 |
| EC Number |
|
| 49775 | |
| KEGG | |
| MeSH | gamma-Aminobutyric+Acid |
PubChem CID
|
|
| RTECS number |
|
| UNII | |
CompTox Dashboard (EPA)
|
|
| |
| |
| Properties | |
| C4H9NO2 | |
| Molar mass | 103.121 g·mol−1 |
| Appearance | white microcrystalline powder |
| Density | 1.11 g/mL |
| Melting point | 203.7 °C (398.7 °F; 476.8 K) |
| Boiling point | 247.9 °C (478.2 °F; 521.0 K) |
| Freely soluble[1][2] | |
| log P | −3.17 |
| Acidity (pKa) |
|
| Hazards | |
| Occupational safety and health (OHS/OSH): | |
Main hazards
|
Irritant, Harmful |
| Lethal dose or concentration (LD, LC): | |
LD50 (median dose)
|
12,680 mg/kg (mouse, oral) |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
| |
GABA (gamma-aminobutyric acid, γ-aminobutyric acid) is the chief inhibitory neurotransmitter in the developmentally mature mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system.
GABA is sold as a dietary supplement in many countries. It has been traditionally thought that exogenous GABA (i.e., taken as a supplement) does not cross the blood–brain barrier, but data obtained from more recent research (2010s) in rats describes the notion as being unclear.[4][5]
The carboxylate form of GABA is γ-aminobutyrate.
Function
Neurotransmitter
Two general classes of GABA receptor are known:[6]
- GABAA in which the receptor is part of a ligand-gated ion channel complex[7]
- GABAB metabotropic receptors, which are G protein-coupled receptors that open or close ion channels via intermediaries (G proteins)
Neurons that produce GABA as their output are called GABAergic neurons. In adult vertebrates, GABA is usually considered as the major inhibitory neurotransmitter. It also exhibits excitatory effect via GABAB receptor, in which case, a specific type of voltage dependent calcium channel is activated.[8]
Medium spiny cells are a typical example of inhibitory central nervous system GABAergic cells. In contrast, GABA exhibits both excitatory and inhibitory actions in insects, mediating muscle activation at synapses between nerves and muscle cells, and also the stimulation of certain glands.[9] In mammals, some GABAergic neurons, such as chandelier cells, are also able to excite their glutamatergic counterparts.[10] In addition to fast-acting phasic inhibition, small amounts of extracellular GABA can induce slow timescale tonic inhibition on neurons.[11]
GABAA receptors are ligand-activated chloride channels: when activated by GABA, they allow the flow of chloride ions across the membrane of the cell.[7] Whether this chloride flow is depolarizing (makes the voltage across the cell's membrane less negative), shunting (has no effect on the cell's membrane potential), or inhibitory/hyperpolarizing (makes the cell's membrane more negative) depends on the direction of the flow of chloride. When net chloride flows out of the cell, GABA is depolarising; when chloride flows into the cell, GABA is inhibitory or hyperpolarizing. When the net flow of chloride is close to zero, the action of GABA is shunting. Shunting inhibition has no direct effect on the membrane potential of the cell; however, it reduces the effect of any coincident synaptic input by reducing the electrical resistance of the cell's membrane.
Shunting inhibition can "override" the excitatory effect of depolarising GABA, resulting in overall inhibition even if the membrane potential becomes less negative. It was thought that a developmental switch in the molecular machinery controlling the concentration of chloride inside the cell changes the functional role of GABA between neonatal and adult stages. As the brain develops into adulthood, GABA's role changes from excitatory to inhibitory.[12]
Brain development
GABA is an inhibitory transmitter in the mature brain; its actions were thought to be primarily excitatory in the developing brain.[12][13] The gradient of chloride was reported to be reversed in immature neurons, with its reversal potential higher than the resting membrane potential of the cell; activation of a GABA-A receptor thus leads to efflux of Cl− ions from the cell (that is, a depolarizing current). The differential gradient of chloride in immature neurons was shown to be primarily due to the higher concentration of NKCC1 co-transporters relative to KCC2 co-transporters in immature cells. GABAergic interneurons mature faster in the hippocampus and the GABA machinery appears earlier than glutamatergic transmission. Thus, GABA is considered the major excitatory neurotransmitter in many regions of the brain before the maturation of glutamatergic synapses.[14]
In the developmental stages preceding the formation of synaptic contacts, GABA is synthesized by neurons and acts both as an autocrine (acting on the same cell) and paracrine (acting on nearby cells) signalling mediator.[15][16] The ganglionic eminences also contribute greatly to building up the GABAergic cortical cell population.[17]
GABA regulates the proliferation of neural progenitor cells,[18][19] the migration[20] and differentiation[21][22] the elongation of neurites[23] and the formation of synapses.[24]
GABA also regulates the growth of embryonic and neural stem cells. GABA can influence the development of neural progenitor cells via brain-derived neurotrophic factor (BDNF) expression.[25] GABA activates the GABAA receptor, causing cell cycle arrest in the S-phase, limiting growth.[26]
Beyond the nervous system
Besides the nervous system, GABA is also produced at relatively high levels in the insulin-producing beta cells (β-cells) of the pancreas. The β-cells secrete GABA along with insulin and the GABA binds to GABA receptors on the neighboring islet alpha cells (α-cells) and inhibits them from secreting glucagon (which would counteract insulin's effects).[28]
GABA can promote the replication and survival of β-cells[29][30][31] and also promote the conversion of α-cells to β-cells, which may lead to new treatments for diabetes.[32]
Alongside GABAergic mechanisms, GABA has also been detected in other peripheral tissues including intestines, stomach, fallopian tubes, uterus, ovaries, testicles, kidneys, urinary bladder, the lungs and liver, albeit at much lower levels than in neurons or β-cells.[33]
Experiments on mice have shown that hypothyroidism induced by fluoride poisoning can be halted by administering GABA. The test also found that the thyroid recovered naturally without further assistance after the fluoride had been expelled by the GABA.[34]
Immune cells express receptors for GABA[35][36] and administration of GABA can suppress inflammatory immune responses and promote "regulatory" immune responses, such that GABA administration has been shown to inhibit autoimmune diseases in several animal models.[29][35][37][38]
In 2018, GABA was shown to regulate secretion of a greater number of cytokines. In plasma of T1D patients, levels of 26 cytokines are increased and of those, 16 are inhibited by GABA in the cell assays.[39]
In 2007, an excitatory GABAergic system was described in the airway epithelium. The system is activated by exposure to allergens and may participate in the mechanisms of asthma.[40] GABAergic systems have also been found in the testis[41] and in the eye lens.[42]
Structure and conformation
GABA is found mostly as a zwitterion (i.e., with the carboxyl group deprotonated and the amino group protonated). Its conformation depends on its environment. In the gas phase, a highly folded conformation is strongly favored due to the electrostatic attraction between the two functional groups. The stabilization is about 50 kcal/mol, according to quantum chemistry calculations. In the solid state, an extended conformation is found, with a trans conformation at the amino end and a gauche conformation at the carboxyl end. This is due to the packing interactions with the neighboring molecules. In solution, five different conformations, some folded and some extended, are found as a result of solvation effects. The conformational flexibility of GABA is important for its biological function, as it has been found to bind to different receptors with different conformations. Many GABA analogues with pharmaceutical applications have more rigid structures in order to control the binding better.[43][44]
History
GABA was first synthesized in 1883; it was first known only as a plant and microbe metabolic product.[45]
In 1950, Washington University School of Medicine researchers Eugene Roberts and Sam Frankel used newly-developed techniques of chromatography to analyze protein-free extracts of mammalian brain. They discovered that GABA is metabolized from glutamic acid and accumulates in the mammalian central nervous system.[46][47]
There was not much further research into the substance until 1957; Canadian researchers identified GABA as the mysterious component (termed Factor I by its discoverers in 1954) of brain and spinal cord extracts which inhibited crayfish neurons.[46][48]
In 1959, it was shown that, at an inhibitory synapse on crayfish muscle fibers, GABA acts through stimulation of the inhibitory nerve. Both inhibition by nerve stimulation and by applied GABA are blocked by picrotoxin.[49]
Biosynthesis
GABA is primarily synthesized from glutamate via the enzyme glutamate decarboxylase (GAD) with pyridoxal phosphate (the active form of vitamin B6) as a cofactor. This process converts glutamate (the principal excitatory neurotransmitter) into GABA (the principal inhibitory neurotransmitter).[50][51]
GABA can also be synthesized from putrescine[52][53] by diamine oxidase and aldehyde dehydrogenase.[52]
Historically it was thought that exogenous GABA did not penetrate the blood–brain barrier,[4] but more current research[5] describes the notion as being unclear pending further research.
Metabolism
GABA transaminase enzymes catalyze the conversion of 4-aminobutanoic acid (GABA) and 2-oxoglutarate (α-ketoglutarate) into succinic semialdehyde and glutamate. Succinic semialdehyde is then oxidized into succinic acid by succinic semialdehyde dehydrogenase and as such enters the citric acid cycle as a usable source of energy.[54]
Pharmacology
Receptors as drug target
Drugs that act as allosteric modulators of GABA receptors (known as GABA analogues or GABAergic drugs), or increase the available amount of GABA, typically have relaxing, anti-anxiety, and anti-convulsive effects (with equivalent efficacy to lamotrigine based on studies of mice).[55][56] Many of the substances below are known to cause anterograde amnesia and retrograde amnesia.[57]
GABA and anesthetics
Lots of general anesthetics work by changing how GABA acts in the brain[58]. Drugs such as propofol, etomidate, barbiturates, and many gases like isoflurane and sevoflurane cause GABAa receptors to become more active[59]. When these receptors become more active, GABA open chloride channels for a longer time, which causes nerve cells to be less likely to send signals. GABAa receptors can become desensitized to GABA and stop opening when the ligand is attached. Anesthetics work in two main ways: enhancing the effectiveness of GABA molecules, and manipulating the GABAa receptor to become less susceptible to desensitization. The slowing of brain activity from increased chloride movement causes the body to calm down, become drowsy, and eventually end up in an unconscious state that is needed for surgery[60]. Some anesthetics can even activate GABAa receptors without GABA even being present. The various types of GABA receptors have drug specific reactions which cause the differing effects of anesthetics.
Adding exogenous GABA
In general, GABA does not cross the blood–brain barrier,[4] although certain areas of the brain that have no effective blood–brain barrier, such as the periventricular nucleus, can be reached by drugs such as systemically injected GABA.[61] At least one study suggests that orally administered GABA increases the amount of human growth hormone (HGH).[62] GABA directly injected to the brain has been reported to have both stimulatory and inhibitory effects on the production of growth hormone, depending on the physiology of the individual.[61] Consequently, considering the potential biphasic effects of GABA on growth hormone production, as well as other safety concerns, its usage is not recommended during pregnancy and lactation.[63]
GABA enhances the catabolism of serotonin into N-acetylserotonin (the precursor of melatonin) in rat pineal glands (removed from the body, ex vivo).[64] It also depolarizes the GnRH-producing neurons ex vivo via their GABAA receptors. Melatonin modulates the strength of deploarization caused by the GABAA receptors ex vivo (rat brain tissue). It is thus suspected that GABA is involved in the synthesis of melatonin and thus might exert regulatory effects on sleep and reproductive functions.[65]
Chemistry
Although in chemical terms, GABA is an amino acid (as it has both a primary amine and a carboxylic acid functional group), it is rarely referred to as such in the professional, scientific, or medical community. By convention the term "amino acid", when used without a qualifier, refers specifically to an alpha amino acid. GABA is not an alpha amino acid, meaning the amino group is not attached to the alpha carbon. Nor is it incorporated into proteins as are many alpha-amino acids.[66]
GABAergic drugs
GABAA receptor ligands are shown in the following table.[nb 1]
| Activity at GABAA | Ligand |
|---|---|
| Orthosteric agonist | Muscimol,[67] GABA,[67] gaboxadol (THIP),[67] isoguvacine, progabide, piperidine-4-sulfonic acid (partial agonist) |
| Positive allosteric modulators | Barbiturates,[68] benzodiazepines,[69] neuroactive steroids,[70] niacin/niacinamide,[71] nonbenzodiazepines (i.e., z-drugs, e.g., zolpidem), etomidate,[72] alcohol (ethanol),[73][74][75] methaqualone, propofol, stiripentol,[76] and anaesthetics[67] (including volatile anaesthetics) |
| Orthosteric (competitive) antagonist | bicuculline,[67] gabazine,[77] thujone,[78] flumazenil[79] |
| Uncompetitive antagonist (e.g., channel blocker) | cicutoxin |
| Negative allosteric modulators | furosemide, oenanthotoxin, amentoflavone |
GABAergic pro-drugs include chloral hydrate, which is metabolised to trichloroethanol,[80] which then acts via the GABAA receptor.[81]
The plant kava contains GABAergic compounds, including kavain, dihydrokavain, methysticin, dihydromethysticin and yangonin.[82]
 | This section needs more reliable medical references for verification or relies too heavily on primary sources. (June 2015) |
Other GABAergic modulators include:
- GABAB receptor ligands.[citation needed]
- GABA reuptake inhibitors: deramciclane, hyperforin, tiagabine.[citation needed]
- GABA transaminase inhibitors: gabaculine, phenelzine, valproate, vigabatrin, lemon balm (Melissa officinalis).[84]
- GABA analogues: pregabalin, gabapentin,[85] picamilon, progabide[citation needed]
4-Amino-1-butanol is a biochemical precursor of GABA and can be converted into GABA by the actions of aldehyde reductase (ALR) and aldehyde dehydrogenase (ALDH) with γ-aminobutyraldehyde (GABAL) as a metabolic intermediate.[86]
In plants
GABA is also found in plants.[87][88] It is the most abundant amino acid in the apoplast of tomatoes.[89] Evidence also suggests a role in cell signalling in plants.[90][91] Recently, a new enzyme technology has been developed to enhance the GABA content of protein-rich seeds such as Andean lupine or tarwi (Lupinus mutabilis) and varieties of quinoa (Chenopodium quinoa) and its relative, cañahua (Chenopodium pallidicaule).[92]
See also
- 3-Aminoisobutyric acid
- 4-aminobutyrate transaminase (GABA-transaminase) deficiency
- GABA analogue
- GABA receptor
- GABA tea
- Giant depolarizing potential
- Spastic diplegia, a GABA deficiency neuromuscular neuropathology
- Spasticity
- Succinic semialdehyde dehydrogenase deficiency
- Taurine
Notes
- ^ Many more GABAA ligands are listed at Template:GABA receptor modulators and at GABAA receptor#Ligands.
References
- ^ "SDS - Gamma-aminobutyric acid". Retrieved 28 October 2025.
- ^ "Human Metabolome Database - Gamma-aminobutyric acid". Retrieved 28 October 2025.
- ^ Haynes, William M., ed. (2016). CRC Handbook of Chemistry and Physics (97th ed.). CRC Press. pp. 5–88. ISBN 978-1-4987-5428-6.
- ^ a b c Kuriyama K, Sze PY (January 1971). "Blood–brain barrier to H3-γ-aminobutyric acid in normal and amino oxyacetic acid-treated animals". Neuropharmacology. 10 (1): 103–108. doi:10.1016/0028-3908(71)90013-X. PMID 5569303.
- ^ a b Boonstra E, de Kleijn R, Colzato LS, Alkemade A, Forstmann BU, Nieuwenhuis S (2015). "Neurotransmitters as food supplements: the effects of GABA on brain and behavior". Front Psychol. 6: 1520. doi:10.3389/fpsyg.2015.01520. PMC 4594160. PMID 26500584.
- ^ Marescaux, C.; Vergnes, M.; Bernasconi, R. (2013-03-08). Generalized Non-Convulsive Epilepsy: Focus on GABA-B Receptors. Springer Science & Business Media. ISBN 978-3-7091-9206-1.
- ^ a b Phulera, Swastik; Zhu, Hongtao; Yu, Jie; Claxton, Derek P.; Yoder, Nate; Yoshioka, Craig; Gouaux, Eric (2018-07-25). "Cryo-EM structure of the benzodiazepine-sensitive α1β1γ2S tri-heteromeric GABAA receptor in complex with GABA". eLife. 7 e39383. doi:10.7554/eLife.39383. ISSN 2050-084X. PMC 6086659. PMID 30044221.
- ^ Zhang, Juen; Tan, Lubin; Ren, Yuqi; Liang, Jingwen; Lin, Rui; Feng, Qiru; Zhou, Jingfeng; Hu, Fei; Ren, Jing; Wei, Chao; Yu, Tao; Zhuang, Yinghua; Bettler, Bernhard; Wang, Fengchao; Luo, Minmin (July 2016). "Presynaptic Excitation via GABA B Receptors in Habenula Cholinergic Neurons Regulates Fear Memory Expression". Cell. 166 (3): 716–728. doi:10.1016/j.cell.2016.06.026. PMID 27426949.
- ^ Ffrench-Constant RH, Rocheleau TA, Steichen JC, Chalmers AE (June 1993). "A point mutation in a Drosophila GABA receptor confers insecticide resistance". Nature. 363 (6428): 449–51. Bibcode:1993Natur.363..449F. doi:10.1038/363449a0. PMID 8389005. S2CID 4334499.
- ^ Szabadics J, Varga C, Molnár G, Oláh S, Barzó P, Tamás G (January 2006). "Excitatory effect of GABAergic axo-axonic cells in cortical microcircuits". Science. 311 (5758): 233–235. Bibcode:2006Sci...311..233S. doi:10.1126/science.1121325. PMID 16410524. S2CID 40744562.
- ^ Koh, Wuhyun; Kwak, Hankyul; Cheong, Eunji; Lee, C. Justin (2023-07-26). "GABA tone regulation and its cognitive functions in the brain". Nature Reviews Neuroscience. 24 (9): 523–539. doi:10.1038/s41583-023-00724-7. ISSN 1471-003X. PMID 37495761. S2CID 260201740.
- ^ a b Li K, Xu E (June 2008). "The role and the mechanism of γ-aminobutyric acid during central nervous system development". Neurosci Bull. 24 (3): 195–200. doi:10.1007/s12264-008-0109-3. PMC 5552538. PMID 18500393.
- ^ Ben-Ari Y, Gaiarsa JL, Tyzio R, Khazipov R (October 2007). "GABA: a pioneer transmitter that excites immature neurons and generates primitive oscillations". Physiol. Rev. 87 (4): 1215–1284. Bibcode:2007PhyRv..87.1215B. doi:10.1152/physrev.00017.2006. PMID 17928584.
- ^ Schousboe, Arne; Sonnewald, Ursula (2016-11-25). The Glutamate/GABA-Glutamine Cycle: Amino Acid Neurotransmitter Homeostasis. Springer. ISBN 978-3-319-45096-4.
- ^ Purves D, Fitzpatrick D, Hall WC, Augustine GJ, Lamantia AS, eds. (2007). Neuroscience (4th ed.). Sunderland, Mass: Sinauer. pp. 135, box 6D. ISBN 978-0-87893-697-7.
- ^ Jelitai M, Madarasz E (2005). "The role of GABA in the early neuronal development". GABA in Autism and Related Disorders. International Review of Neurobiology. Vol. 71. pp. 27–62. doi:10.1016/S0074-7742(05)71002-3. ISBN 978-0-12-366872-1. PMID 16512345.
- ^ Marín O, Rubenstein JL (November 2001). "A long, remarkable journey: tangential migration in the telencephalon". Nat. Rev. Neurosci. 2 (11): 780–90. doi:10.1038/35097509. PMID 11715055. S2CID 5604192.
- ^ LoTurco JJ, Owens DF, Heath MJ, Davis MB, Kriegstein AR (December 1995). "GABA and glutamate depolarize cortical progenitor cells and inhibit DNA synthesis". Neuron. 15 (6): 1287–1298. doi:10.1016/0896-6273(95)90008-X. PMID 8845153. S2CID 1366263.
- ^ Haydar TF, Wang F, Schwartz ML, Rakic P (August 2000). "Differential modulation of proliferation in the neocortical ventricular and subventricular zones". J. Neurosci. 20 (15): 5764–74. doi:10.1523/JNEUROSCI.20-15-05764.2000. PMC 3823557. PMID 10908617.
- ^ Behar TN, Schaffner AE, Scott CA, O'Connell C, Barker JL (August 1998). "Differential response of cortical plate and ventricular zone cells to GABA as a migration stimulus". J. Neurosci. 18 (16): 6378–87. doi:10.1523/JNEUROSCI.18-16-06378.1998. PMC 6793175. PMID 9698329.
- ^ Ganguly K, Schinder AF, Wong ST, Poo M (May 2001). "GABA itself promotes the developmental switch of neuronal GABAergic responses from excitation to inhibition". Cell. 105 (4): 521–32. doi:10.1016/S0092-8674(01)00341-5. PMID 11371348. S2CID 8615968.
- ^ Barbin G, Pollard H, Gaïarsa JL, Ben-Ari Y (April 1993). "Involvement of GABAA receptors in the outgrowth of cultured hippocampal neurons". Neurosci. Lett. 152 (1–2): 150–154. doi:10.1016/0304-3940(93)90505-F. PMID 8390627. S2CID 30672030.
- ^ Maric D, Liu QY, Maric I, Chaudry S, Chang YH, Smith SV, Sieghart W, Fritschy JM, Barker JL (April 2001). "GABA expression dominates neuronal lineage progression in the embryonic rat neocortex and facilitates neurite outgrowth via GABA(A) autoreceptor/Cl− channels". J. Neurosci. 21 (7): 2343–60. doi:10.1523/JNEUROSCI.21-07-02343.2001. PMC 6762405. PMID 11264309.
- ^ Ben-Ari Y (September 2002). "Excitatory actions of gaba during development: the nature of the nurture". Nat. Rev. Neurosci. 3 (9): 728–739. doi:10.1038/nrn920. PMID 12209121. S2CID 8116740.
- ^ Obrietan K, Gao XB, Van Den Pol AN (August 2002). "Excitatory actions of GABA increase BDNF expression via a MAPK-CREB-dependent mechanism—a positive feedback circuit in developing neurons". J. Neurophysiol. 88 (2): 1005–15. doi:10.1152/jn.2002.88.2.1005. PMID 12163549.
- ^ Wang DD, Kriegstein AR, Ben-Ari Y (2008). "GABA regulates stem cell proliferation before nervous system formation". Epilepsy Curr. 8 (5): 137–9. doi:10.1111/j.1535-7511.2008.00270.x. PMC 2566617. PMID 18852839.
- ^ Popp A, Urbach A, Witte OW, Frahm C (2009). Reh TA (ed.). "Adult and embryonic GAD transcripts are spatiotemporally regulated during postnatal development in the rat brain". PLoS ONE. 4 (2) e4371. Bibcode:2009PLoSO...4.4371P. doi:10.1371/journal.pone.0004371. PMC 2629816. PMID 19190758.
- ^ Rorsman P, Berggren PO, Bokvist K, Ericson H, Möhler H, Ostenson CG, Smith PA (1989). "Glucose-inhibition of glucagon secretion involves activation of GABAA-receptor chloride channels". Nature. 341 (6239): 233–6. Bibcode:1989Natur.341..233R. doi:10.1038/341233a0. PMID 2550826. S2CID 699135.
- ^ a b Soltani N, Qiu H, Aleksic M, Glinka Y, Zhao F, Liu R, Li Y, Zhang N, Chakrabarti R, Ng T, Jin T, Zhang H, Lu WY, Feng ZP, Prud'homme GJ, Wang Q (2011). "GABA exerts protective and regenerative effects on islet beta cells and reverses diabetes". Proc. Natl. Acad. Sci. U.S.A. 108 (28): 11692–7. Bibcode:2011PNAS..10811692S. doi:10.1073/pnas.1102715108. PMC 3136292. PMID 21709230.
- ^ Tian J, Dang H, Chen Z, Guan A, Jin Y, Atkinson MA, Kaufman DL (2013). "γ-Aminobutyric acid regulates both the survival and replication of human β-cells". Diabetes. 62 (11): 3760–5. doi:10.2337/db13-0931. PMC 3806626. PMID 23995958.
- ^ Purwana I, Zheng J, Li X, Deurloo M, Son DO, Zhang Z, Liang C, Shen E, Tadkase A, Feng ZP, Li Y, Hasilo C, Paraskevas S, Bortell R, Greiner DL, Atkinson M, Prud'homme GJ, Wang Q (2014). "GABA promotes human β-cell proliferation and modulates glucose homeostasis". Diabetes. 63 (12): 4197–205. doi:10.2337/db14-0153. PMID 25008178.
- ^ Ben-Othman N, Vieira A, Courtney M, Record F, Gjernes E, Avolio F, Hadzic B, Druelle N, Napolitano T, Navarro-Sanz S, Silvano S, Al-Hasani K, Pfeifer A, Lacas-Gervais S, Leuckx G, Marroquí L, Thévenet J, Madsen OD, Eizirik DL, Heimberg H, Kerr-Conte J, Pattou F, Mansouri A, Collombat P (2017). "Long-Term GABA Administration Induces Alpha Cell-Mediated Beta-like Cell Neogenesis". Cell. 168 (1–2): 73–85.e11. doi:10.1016/j.cell.2016.11.002. PMID 27916274.
- ^ Erdö SL, Wolff JR (February 1990). "γ-Aminobutyric acid outside the mammalian brain". J. Neurochem. 54 (2): 363–72. doi:10.1111/j.1471-4159.1990.tb01882.x. PMID 2405103. S2CID 86144218.
- ^ Yang H, Xing R, Liu S, Yu H, Li P (2016). "γ-Aminobutyric acid ameliorates fluoride-induced hypothyroidism in male Kunming mice". Life Sciences. 146: 1–7. doi:10.1016/j.lfs.2015.12.041. PMID 26724496.
- ^ a b Tian J, Chau C, Hales TG, Kaufman DL (1999). "GABAA receptors mediate inhibition of T cell responses". J. Neuroimmunol. 96 (1): 21–8. doi:10.1016/s0165-5728(98)00264-1. PMID 10227421. S2CID 3006821.
- ^ Mendu SK, Bhandage A, Jin Z, Birnir B (2012). "Different subtypes of GABA-A receptors are expressed in human, mouse and rat T lymphocytes". PLOS ONE. 7 (8) e42959. Bibcode:2012PLoSO...742959M. doi:10.1371/journal.pone.0042959. PMC 3424250. PMID 22927941.
- ^ Tian J, Lu Y, Zhang H, Chau CH, Dang HN, Kaufman DL (2004). "Gamma-aminobutyric acid inhibits T cell autoimmunity and the development of inflammatory responses in a mouse type 1 diabetes model". J. Immunol. 173 (8): 5298–304. doi:10.4049/jimmunol.173.8.5298. PMID 15470076.
- ^ Tian J, Yong J, Dang H, Kaufman DL (2011). "Oral GABA treatment downregulates inflammatory responses in a mouse model of rheumatoid arthritis". Autoimmunity. 44 (6): 465–70. doi:10.3109/08916934.2011.571223. PMC 5787624. PMID 21604972.
- ^ Bhandage AK, Jin Z, Korol SV, Shen Q, Pei Y, Deng Q, Espes D, Carlsson PO, Kamali-Moghaddam M, Birnir B (April 2018). "+ T Cells and Is Immunosuppressive in Type 1 Diabetes". eBioMedicine. 30: 283–294. doi:10.1016/j.ebiom.2018.03.019. PMC 5952354. PMID 29627388.
- ^ Xiang YY, Wang S, Liu M, Hirota JA, Li J, Ju W, Fan Y, Kelly MM, Ye B, Orser B, O'Byrne PM, Inman MD, Yang X, Lu WY (July 2007). "A GABAergic system in airway epithelium is essential for mucus overproduction in asthma". Nat. Med. 13 (7): 862–7. doi:10.1038/nm1604. PMID 17589520. S2CID 2461757.
- ^ Payne AH, Hardy MH (2007). The Leydig cell in health and disease. Humana Press. ISBN 978-1-58829-754-9.
- ^ Kwakowsky A, Schwirtlich M, Zhang Q, Eisenstat DD, Erdélyi F, Baranyi M, Katarova ZD, Szabó G (December 2007). "GAD isoforms exhibit distinct spatiotemporal expression patterns in the developing mouse lens: correlation with Dlx2 and Dlx5". Dev. Dyn. 236 (12): 3532–44. doi:10.1002/dvdy.21361. PMID 17969168. S2CID 24188696.
- ^ Majumdar D, Guha S (1988). "Conformation, electrostatic potential and pharmacophoric pattern of GABA (γ-aminobutyric acid) and several GABA inhibitors". Journal of Molecular Structure: THEOCHEM. 180: 125–140. doi:10.1016/0166-1280(88)80084-8.
- ^ Sapse AM (2000). Molecular Orbital Calculations for Amino Acids and Peptides. Birkhäuser. ISBN 978-0-8176-3893-1.[page needed]
- ^ Roth RJ, Cooper JR, Bloom FE (2003). The Biochemical Basis of Neuropharmacology. Oxford [Oxfordshire]: Oxford University Press. p. 106. ISBN 978-0-19-514008-8.
- ^ a b Spiering, Martin J. (December 2018). "The discovery of GABA in the brain". Journal of Biological Chemistry. 293 (49): 19159–19160. doi:10.1074/jbc.cl118.006591. ISSN 0021-9258. PMC 6295731. PMID 30530855.
- ^ Roberts, E.; Frankel, S. (November 1950). "gamma-Aminobutyric acid in brain: its formation from glutamic acid". The Journal of Biological Chemistry. 187 (1): 55–63. doi:10.1016/S0021-9258(19)50929-2. ISSN 0021-9258. PMID 14794689.
- ^ Bazemore, A. W.; Elliott, K. A. C.; Florey, E. (August 1957). "Isolation of Factor I". Journal of Neurochemistry. 1 (4): 334–339. doi:10.1111/j.1471-4159.1957.tb12090.x. ISSN 0022-3042. PMID 13476199.
- ^ W. G. Van der Kloot; J. Robbins (1959). "The effects of GABA and picrotoxin on the junctional potential and the contraction of crayfish muscle". Experientia. 15: 36.
- ^ Petroff OA (December 2002). "GABA and glutamate in the human brain". Neuroscientist. 8 (6): 562–573. doi:10.1177/1073858402238515. PMID 12467378. S2CID 84891972.
- ^ Schousboe A, Waagepetersen HS (2007). "GABA: Homeostatic and pharmacological aspects". Gaba and the Basal Ganglia - from Molecules to Systems. Progress in Brain Research. Vol. 160. pp. 9–19. doi:10.1016/S0079-6123(06)60002-2. ISBN 978-0-444-52184-2. PMID 17499106.
- ^ a b Krantis, Anthony (2000-12-01). "GABA in the Mammalian Enteric Nervous System". Physiology. 15 (6): 284–290. doi:10.1152/physiologyonline.2000.15.6.284. ISSN 1548-9213. PMID 11390928.
- ^ Sequerra, E. B.; Gardino, P.; Hedin-Pereira, C.; de Mello, F. G. (2007-05-11). "Putrescine as an important source of GABA in the postnatal rat subventricular zone". Neuroscience. 146 (2): 489–493. doi:10.1016/j.neuroscience.2007.01.062. ISSN 0306-4522. PMID 17395389. S2CID 43003476.
- ^ Bown AW, Shelp BJ (September 1997). "The Metabolism and Functions of γ-Aminobutyric Acid". Plant Physiol. 115 (1): 1–5. doi:10.1104/pp.115.1.1. PMC 158453. PMID 12223787.
- ^ Foster AC, Kemp JA (February 2006). "Glutamate- and GABA-based CNS therapeutics". Curr Opin Pharmacol. 6 (1): 7–17. doi:10.1016/j.coph.2005.11.005. PMID 16377242.
- ^ Chapouthier G, Venault P (October 2001). "A pharmacological link between epilepsy and anxiety?". Trends Pharmacol. Sci. 22 (10): 491–3. doi:10.1016/S0165-6147(00)01807-1. PMID 11583788.
- ^ Campagna JA, Miller KW, Forman SA (May 2003). "Mechanisms of actions of inhaled anesthetics". N. Engl. J. Med. 348 (21): 2110–24. doi:10.1056/NEJMra021261. PMID 12761368.
- ^ Orser, B. A.; McAdam, L. C.; Roder, S.; MacDonald, J. F. (1998-11-23). "General anaesthetics and their effects on GABAA receptor desensitization". Toxicology Letters. 100–101: 217–224. doi:10.1016/S0378-4274(98)00188-X. ISSN 0378-4274. PMID 10049145.
- ^ Brohan, Janette; Goudra, Basavana G. (Oct 2017). "The Role of GABA Receptor Agonists in Anesthesia and Sedation". CNS Drugs. 31 (10): 845–856. doi:10.1007/s40263-017-0463-7. ISSN 1179-1934. PMID 29039138.
- ^ Lecker, I.; Yin, Y.; Wang, D. S.; Orser, B. A. (2013-06-01). "Potentiation of GABAA receptor activity by volatile anaesthetics is reduced by α5GABAA receptor-preferring inverse agonists". British Journal of Anaesthesia. 110: i73–i81. doi:10.1093/bja/aet038. ISSN 0007-0912. PMC 3732063. PMID 23535829.
- ^ a b Müller EE, Locatelli V, Cocchi D (April 1999). "Neuroendocrine control of growth hormone secretion". Physiol. Rev. 79 (2): 511–607. Bibcode:1999PhyRv..79..511M. doi:10.1152/physrev.1999.79.2.511. PMID 10221989.
- ^ Powers ME, Yarrow JF, McCoy SC, Borst SE (January 2008). "Growth hormone isoform responses to GABA ingestion at rest and after exercise". Medicine and Science in Sports and Exercise. 40 (1): 104–10. doi:10.1249/mss.0b013e318158b518. PMID 18091016. S2CID 24907247.
- ^ Oketch-Rabah HA, Madden EF, Roe AL, Betz JM (August 2021). "United States Pharmacopeia (USP) Safety Review of Gamma-Aminobutyric Acid (GABA)". Nutrients. 13 (8): 2742. doi:10.3390/nu13082742. PMC 8399837. PMID 34444905.
- ^ Balemans MG, Mans D, Smith I, Van Benthem J (1983). "The influence of GABA on the synthesis of N-acetylserotonin, melatonin, O-acetyl-5-hydroxytryptophol and O-acetyl-5-methoxytryptophol in the pineal gland of the male Wistar rat". Reproduction, Nutrition, Development. 23 (1): 151–60. doi:10.1051/rnd:19830114. PMID 6844712.
- ^ Sato S, Yinc C, Teramoto A, Sakuma Y, Kato M (2008). "Sexually dimorphic modulation of GABA(A) receptor currents by melatonin in rats gonadotropin–releasing hormone neurons". The Journal of Physiological Sciences. 58 (5): 317–322. doi:10.2170/physiolsci.rp006208. PMID 18834560.
- ^ Hellier, Jennifer L. (2014-12-16). The Brain, the Nervous System, and Their Diseases [3 volumes]. ABC-CLIO. ISBN 978-1-61069-338-7.
- ^ a b c d e Chua HC, Chebib M (2017). "GABA a Receptors and the Diversity in their Structure and Pharmacology". GABAA Receptors and the Diversity in their Structure and Pharmacology. Advances in Pharmacology. Vol. 79. pp. 1–34. doi:10.1016/bs.apha.2017.03.003. ISBN 978-0-12-810413-2. PMID 28528665. S2CID 41704867.
- ^ Löscher, W.; Rogawski, M. A. (2012). "How theories evolved concerning the mechanism of action of barbiturates". Epilepsia. 53: 12–25. doi:10.1111/epi.12025. PMID 23205959. S2CID 4675696.
- ^ Olsen RW, Betz H (2006). "GABA and glycine". In Siegel GJ, Albers RW, Brady S, Price DD (eds.). Basic Neurochemistry: Molecular, Cellular and Medical Aspects (7th ed.). Elsevier. pp. 291–302. ISBN 978-0-12-088397-4.
- ^
- Herd MB, Belelli D, Lambert JJ (October 2007). "Neurosteroid modulation of synaptic and extrasynaptic GABA(A) receptors". Pharmacology & Therapeutics. 116 (1): 20–34. doi:10.1016/j.pharmthera.2007.03.007. PMID 17531325.
- Hosie AM, Wilkins ME, da Silva HM, Smart TG (November 2006). "Endogenous neurosteroids regulate GABAA receptors through two discrete transmembrane sites". Nature. 444 (7118): 486–9. Bibcode:2006Natur.444..486H. doi:10.1038/nature05324. PMID 17108970. S2CID 4382394.
- Agís-Balboa RC, Pinna G, Zhubi A, Maloku E, Veldic M, Costa E, Guidotti A (September 2006). "Characterization of brain neurons that express enzymes mediating neurosteroid biosynthesis". Proceedings of the National Academy of Sciences of the United States of America. 103 (39): 14602–7. Bibcode:2006PNAS..10314602A. doi:10.1073/pnas.0606544103. PMC 1600006. PMID 16984997.
- Akk G, Shu HJ, Wang C, Steinbach JH, Zorumski CF, Covey DF, Mennerick S (December 2005). "Neurosteroid access to the GABAA receptor". The Journal of Neuroscience. 25 (50): 11605–13. doi:10.1523/JNEUROSCI.4173-05.2005. PMC 6726021. PMID 16354918.
- Belelli D, Lambert JJ (July 2005). "Neurosteroids: endogenous regulators of the GABA(A) receptor". Nature Reviews. Neuroscience. 6 (7): 565–75. doi:10.1038/nrn1703. PMID 15959466. S2CID 12596378.
- Pinna G, Costa E, Guidotti A (June 2006). "Fluoxetine and norfluoxetine stereospecifically and selectively increase brain neurosteroid content at doses that are inactive on 5-HT reuptake". Psychopharmacology. 186 (3): 362–72. doi:10.1007/s00213-005-0213-2. PMID 16432684. S2CID 7799814.
- Dubrovsky BO (February 2005). "Steroids, neuroactive steroids and neurosteroids in psychopathology". Progress in Neuro-Psychopharmacology & Biological Psychiatry. 29 (2): 169–92. doi:10.1016/j.pnpbp.2004.11.001. PMID 15694225. S2CID 36197603.
- Mellon SH, Griffin LD (2002). "Neurosteroids: biochemistry and clinical significance". Trends in Endocrinology and Metabolism. 13 (1): 35–43. doi:10.1016/S1043-2760(01)00503-3. PMID 11750861. S2CID 11605131.
- Puia G, Santi MR, Vicini S, Pritchett DB, Purdy RH, Paul SM, Seeburg PH, Costa E (May 1990). "Neurosteroids act on recombinant human GABAA receptors". Neuron. 4 (5): 759–65. doi:10.1016/0896-6273(90)90202-Q. PMID 2160838. S2CID 12626366.
- Majewska MD, Harrison NL, Schwartz RD, Barker JL, Paul SM (May 1986). "Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor". Science. 232 (4753): 1004–7. Bibcode:1986Sci...232.1004D. doi:10.1126/science.2422758. PMID 2422758.
- Reddy DS, Rogawski MA (2012). "Neurosteroids — Endogenous Regulators of Seizure Susceptibility and Role in the Treatment of Epilepsy". In Noebels JL, Avoli M, Rogawski MA, et al. (eds.). Jasper's Basic Mechanisms of the Epilepsies (4th ed.). Bethesda, Maryland: National Center for Biotechnology Information. PMID 22787590.
- ^ Toraskar, Mrunmayee; Pratima R.P. Singh; Shashank Neve (2010). "Study of GABAergic Agonists" (PDF). Deccan Journal of Pharmacology. 1 (2): 56–69. Archived from the original (PDF) on 2013-10-16. Retrieved 2019-04-01.
- ^ Vanlersberghe, C; Camu, F (2008). "Etomidate and Other Non-Barbiturates". Modern Anesthetics. Handbook of Experimental Pharmacology. Vol. 182. pp. 267–82. doi:10.1007/978-3-540-74806-9_13. ISBN 978-3-540-72813-9. PMID 18175096.
- ^ Dzitoyeva S, Dimitrijevic N, Manev H (2003). "γ-aminobutyric acid B receptor 1 mediates behavior-impairing actions of alcohol in Drosophila: adult RNA interference and pharmacological evidence". Proc. Natl. Acad. Sci. U.S.A. 100 (9): 5485–5490. Bibcode:2003PNAS..100.5485D. doi:10.1073/pnas.0830111100. PMC 154371. PMID 12692303.
- ^ Mihic SJ, Ye Q, Wick MJ, Koltchine VV, Krasowski MD, Finn SE, Mascia MP, Valenzuela CF, Hanson KK, Greenblatt EP, Harris RA, Harrison NL (1997). "Sites of alcohol and volatile anaesthetic action on GABAA and glycine receptors". Nature. 389 (6649): 385–389. Bibcode:1997Natur.389..385M. doi:10.1038/38738. PMID 9311780. S2CID 4393717.
- ^ Source unclear. One of the following:
- Boehm SL, Ponomarev I, Jennings AW, Whiting PJ, Rosahl TW, Garrett EM, Blednov YA, Harris RA (2004). "γ-Aminobutyric acid a receptor subunit mutant mice: New perspectives on alcohol actions". Biochemical Pharmacology. 67 (8): 1581–1602. doi:10.1016/j.bcp.2004.07.023. PMID 17175815.
- Boehm SL, Ponomarev I, Blednov YA, Harris RA (2006). "From Gene to Behavior and Back Again: New Perspectives on GABAA Receptor Subunit Selectivity of Alcohol Actions". In Enna SJ (ed.). GABA. Advances in Pharmacology. Vol. 54. Elsevier. pp. 171–203. doi:10.1016/S1054-3589(06)54008-6. ISBN 978-0-12-032957-1. PMID 17175815.
- ^ Fisher JL (January 2009). "The anti-convulsant stiripentol acts directly on the GABA(A) receptor as a positive allosteric modulator". Neuropharmacology. 56 (1): 190–7. doi:10.1016/j.neuropharm.2008.06.004. PMC 2665930. PMID 18585399.
- ^ Ueno, S; Bracamontes, J; Zorumski, C; Weiss, DS; Steinbach, JH (1997). "Bicuculline and gabazine are allosteric inhibitors of channel opening of the GABAA receptor". The Journal of Neuroscience. 17 (2): 625–34. doi:10.1523/jneurosci.17-02-00625.1997. PMC 6573228. PMID 8987785.
- ^ Olsen RW (April 2000). "Absinthe and gamma-aminobutyric acid receptors". Proc. Natl. Acad. Sci. U.S.A. 97 (9): 4417–8. Bibcode:2000PNAS...97.4417O. doi:10.1073/pnas.97.9.4417. PMC 34311. PMID 10781032.
- ^ Whitwam, J. G.; Amrein, R. (1995-01-01). "Pharmacology of flumazenil". Acta Anaesthesiologica Scandinavica. Supplementum. 108: 3–14. doi:10.1111/j.1399-6576.1995.tb04374.x. ISSN 0515-2720. PMID 8693922. S2CID 24494744.
- ^ Jira, Reinhard; Kopp, Erwin; McKusick, Blaine C.; Röderer, Gerhard; Bosch, Axel; Fleischmann, Gerald. "Chloroacetaldehydes". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a06_527.pub2. ISBN 978-3-527-30673-2.
- ^ Lu, J.; Greco, M. A. (2006). "Sleep circuitry and the hypnotic mechanism of GABAA drugs". Journal of Clinical Sleep Medicine. 2 (2): S19–S26. doi:10.5664/jcsm.26527. PMID 17557503.
- ^ Singh YN, Singh NN (2002). "Therapeutic potential of kava in the treatment of anxiety disorders". CNS Drugs. 16 (11): 731–43. doi:10.2165/00023210-200216110-00002. PMID 12383029. S2CID 34322458.
- ^ Dimitrijevic N, Dzitoyeva S, Satta R, Imbesi M, Yildiz S, Manev H (2005). "Drosophila GABAB receptors are involved in behavioral effects of gamma-hydroxybutyric acid (GHB)". Eur. J. Pharmacol. 519 (3): 246–252. doi:10.1016/j.ejphar.2005.07.016. PMID 16129424.
- ^ Awad R, Muhammad A, Durst T, Trudeau VL, Arnason JT (August 2009). "Bioassay-guided fractionation of lemon balm (Melissa officinalis L.) using an in vitro measure of GABA transaminase activity". Phytother Res. 23 (8): 1075–81. doi:10.1002/ptr.2712. PMID 19165747. S2CID 23127112.
- ^ Celikyurt IK, Mutlu O, Ulak G, Akar FY, Erden F (2011). "Gabapentin, A GABA analogue, enhances cognitive performance in mice". Neuroscience Letters. 492 (2): 124–8. doi:10.1016/j.neulet.2011.01.072. PMID 21296127. S2CID 8303292.
- ^ Storer, R. James; Ferrante, Antonio (10 October 1997). "Radiochemical Assay of Diamine Oxidase". Polyamine Protocols. Methods in Molecular Biology. Vol. 79. New Jersey: Humana Press. pp. 91–96. doi:10.1385/0-89603-448-8:91. ISBN 978-0-89603-448-8. PMID 9463822.
- ^ Ramesh SA, Tyerman SD, Xu B, Bose J, Kaur S, Conn V, Domingos P, Ullah S, Wege S, Shabala S, Feijó JA, Ryan PR, Gilliham M, Gillham M (2015). "GABA signalling modulates plant growth by directly regulating the activity of plant-specific anion transporters". Nat Commun. 6 7879. Bibcode:2015NatCo...6.7879R. doi:10.1038/ncomms8879. PMC 4532832. PMID 26219411.
- ^ Ramesh SA, Tyerman SD, Gilliham M, Xu B (2016). "γ-Aminobutyric acid (GABA) signalling in plants". Cell. Mol. Life Sci. 74 (9): 1577–1603. doi:10.1007/s00018-016-2415-7. hdl:2440/124330. PMC 11107511. PMID 27838745. S2CID 19475505.
- ^ Park DH, Mirabella R, Bronstein PA, Preston GM, Haring MA, Lim CK, Collmer A, Schuurink RC (October 2010). "Mutations in γ-aminobutyric acid (GABA) transaminase genes in plants or Pseudomonas syringae reduce bacterial virulence". Plant J. 64 (2): 318–30. doi:10.1111/j.1365-313X.2010.04327.x. PMID 21070411.
- ^ Bouché N, Fromm H (March 2004). "GABA in plants: just a metabolite?". Trends Plant Sci. 9 (3): 110–5. doi:10.1016/j.tplants.2004.01.006. PMID 15003233.
- ^ Roberts MR (September 2007). "Does GABA Act as a Signal in Plants?: Hints from Molecular Studies". Plant Signal Behav. 2 (5): 408–9. Bibcode:2007PlSiB...2..408R. doi:10.4161/psb.2.5.4335. PMC 2634229. PMID 19704616.
- ^ Ibieta, Gabriela; Ortiz-Sempértegui, Jimena; Peñarrieta, J. Mauricio; Linares-Pastén, Javier A. (March 2025). "Enhancing the functional value of Andean food plants: Enzymatic production of γ-aminobutyric acid from tarwi, cañihua and quinoa real seeds' proteins". LWT. 220 117564. doi:10.1016/j.lwt.2025.117564.
External links
- Smart TG, Stephenson FA (2019). "A half century of γ-aminobutyric acid". Brain Neurosci Adv. 3 2398212819858249. doi:10.1177/2398212819858249. PMC 7058221. PMID 32166183.
- Parviz M, Vogel K, Gibson KM, Pearl PL (2014-11-25). "Disorders of GABA metabolism: SSADH and GABA-transaminase deficiencies". Journal of Pediatric Epilepsy. 3 (4): 217–227. doi:10.3233/PEP-14097. PMC 4256671. PMID 25485164.
Clinical disorders known to affect inherited GABA metabolism
- Gamma-aminobutyric acid MS Spectrum
- Scholarpedia article on GABA
- List of GABA neurons on NeuroLex.org
- Effects of Oral Gamma-Aminobutyric Acid (GABA) Administration on Stress and Sleep in Humans: A Systematic Review
| International | |
|---|---|
| National | |
| Other | |
