γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the adult brain. Published values for γ-Aminobutyric acid EC50 range from 6.6μM – 107μM [1]. γ-Aminobutyric acid plays a role in fast inhibitory synaptic transmission mainly through cytosolic-mediated presynaptic γ-Aminobutyric acid release and postsynaptic activation of low-affinity GABAA receptors (GABAAR) [2]. γ-Aminobutyric acid plays an important role not only in the brain but also in different metabolic organs [3]. Therefore, γ-Aminobutyric acid is commonly used in studies such as multiple neurologic and metabolic diseases.
In vitro, γ-Aminobutyric acid (100μM) effectively reduced glutathione (GSH) depletion and the activities of antioxidant enzymes such as catalase (CAT) and superoxide dismutase (SOD) in C2C12 myoblasts [4]. γ-Aminobutyric acid at 10mM or lower concentrations showed no significant toxicity in MC3T3-E1 cells, and 20mM or higher concentrations resulted in significant cell death [5]. γ-Aminobutyric acid (100μM and 200μM) effectively reversed the inhibitory effect of H2O2 (100μM) on the proliferation of HUVECs [6].
In vivo, γ-Aminobutyric acid was administered orally by force-feeding to Sprague-Dawley rats for 13 weeks at doses of 500, 1250, and 2500mg/kg/day, and there were no toxicologically significant changes in clinical signs, hematology, clinical chemistry, and histopathological changes in rats, indicating that the rats tolerated γ-Aminobutyric acid at doses up to 2500mg/kg/day [7]. γ-Aminobutyric acid (500μmol [50mg]) was intraperitoneally injected into C57BL/6NHsd mice for 7 days, followed by 500μg of tumor necrosis factor-α (TNF-α) and 20mg of D-galactosamine intraperitoneally to induce acute hepatic failure in the mice, which was induced 4-5h after the injection using Western blot and immunohistochemistry and histopathology to analyze the proteins present in the blood samples and liver tissues of the mice showed that γ-Aminobutyric acid can inhibit apoptosis through the STAT3 signaling pathway [8].
References:
[1] Zhu, S.e.a.S.o.a.h.s.G.r.N.v., 7712 (2018): 67-72. doi:10.1038/s41586-018-0255-3.
[2] Koh W, K.H., Cheong E, Lee CJ, GABA tone regulation and its cognitive functions in the brain. Nat Rev Neurosci, 2023 Sep;24(9):523-539.
[3] Kim, K., and Haejin Yoon, Gamma-Aminobutyric Acid Signaling in Damage Response, Metabolism, and Disease. International journal of molecular sciences, vol. 24,5 4584. 26 Feb. 2023.
[4] Choe H, L.H., Lee J, Kim Y. Protective effect of gamma-aminobutyric acid against oxidative stress by inducing phase II enzymes in C2C12 myoblast cells. J Food Biochem. 2021 Apr;45(4):e13639. doi: 10.1111/jfbc.13639. Epub 2021 Feb 3. PMID: 33533516.
[5] Arachchilage Hasitha Maduranga Karunarathne W, H.C.Y., Lee MH, Kang CH, Kim GY. Gamma-aminobutyric acid (GABA)-mediated bone formation and its implications for anti-osteoporosis strategies: Exploring the relation between GABA and GABA receptors. Biochem Pharmacol. 2023 Dec;218:115888. doi: 10.1016/j.bcp.2023.115888. Epub 2023 Oct 29. PMID: 38084676.
[6] Zhu Z, S.Z., Xie C, Gong W, Hu Z, Peng Y. A novel mechanism of Gamma-aminobutyric acid (GABA) protecting human umbilical vein endothelial cells (HUVECs) against H2O2-induced oxidative injury. Comp Biochem Physiol C Toxicol Pharmacol. 2019 Mar;217:68-75. doi: 10.1016/j.cbpc.2018.11.018. Epub 2018 Nov 27. PMID: 30500452.
[7] Takeshima K, Y.A., Yamashita Y, Watabe K, Horie N, et al. Subchronic toxicity evaluation of gamma-aminobutyric acid (GABA) in rats. Food Chem Toxicol 2014:68:128–134.
[8] Hata, T.e.a.G., γ-Aminobutyric Acid, Protects Against Severe Liver Injury.” The Journal of surgical research vol. 236 (2019): 172-183. doi:10.1016/j.jss.2018.11.047.
γ-氨基丁酸（γ-Aminobutyricacid，GABA）是成人大脑中的主要抑制性神经递质。目前已发表的文章中，γ-Aminobutyric acid的EC50为6.6μM–107μM[1]。γ-Aminobutyric acid主要是通过胞吐介导的突触前γ-Aminobutyric acid的释放和突触后低亲和力GABAA受体（GABAAR）的激活在快速抑制性突触传递中发挥作用[2]。γ-Aminobutyric acid不仅在大脑中起着重要作用，还在不同的代谢器官中起着重要作用[3]。因此，γ-Aminobutyric acid常用于多重神经类和代谢疾病等研究中。
在体外，γ-Aminobutyric acid(100μM)可以有效降低C2C12成肌细胞中谷胱甘肽（GSH）的消耗和过氧化氢酶（CAT）和超氧化物歧化酶（SOD）等抗氧化酶的活性[4]。10mM或更低浓度的γ-Aminobutyric acid对MC3T3-E1细胞没有明显的细胞毒性，而20mM或更高浓度的γ-Aminobutyric acid会导致显著的细胞死亡[5]。γ-Aminobutyric acid(100μM和200μM)可以有效逆转H2O2(100μM)对HUVECs增殖的抑制作用[6]。
在体内，γ-Aminobutyric acid以500、1250和2500mg/kg/day的剂量口服强饲给Sprague-Dawley大鼠13周后，大鼠的临床体征、血液学、临床化学和组织病理学变化在毒理学上没有显著变化，说明大鼠对γ-Aminobutyric acid的耐受剂量高达2500mg/kg/day[7]。γ-Aminobutyric acid(500μmol [50mg])腹腔注射C57BL/6NHsd小鼠7天，然后再腹腔注射500μg肿瘤坏死因子α（tumornecrosisfactor-α，TNF-α）和20mgD-半乳糖胺以诱导小鼠急性肝衰竭，注射后4-5小时后，使用Westernblot和免疫组织化学和组织病理学分析小鼠血液样本和肝组织中存在的蛋白质，结果表明γ-Aminobutyric acid可以通过STAT3信号通路抑制细胞凋亡[8]。