GABA is an essential endogenous inhibitory neurotransmitter in the mammalian brain, with the EC50 values of 0.17, 2.1, 2.1, and 1.4μM for α6, α1, α4, and α5 of GABAA receptor, respectively[1]. GABA is loaded into synaptic vesicles via the vesicular inhibitory amino acid transporter and modulates neural excitability to maintain balanced cerebral functions[2]. GABA has been widely used in different animal models to regulate immune responses, interfere with tumor growth, and alleviate anxiety[3].
In vitro, GABA treatment (100µM) for 72 hours significantly inhibited the proliferation of SW480 cells, SW620 cells, and HCT116 cells and induced cell cycle arrest[4]. Treatment of mouse islet B cells with 100µM GABA for 4 days promoted cell proliferation, resulting in increased nuclear expression of p-Akt Ser473 and p-p70S6K Thr421/Ser424[5].
In vivo, GABA treatment via two weeks of oral administration at a dose of 100mg/kg/day significantly improved the metabolic status of rats with polycystic ovary syndrome (PCOs) and reduced body weight, body mass index, and testosterone levels[6]. Intraperitoneal injection of GABA at a dose of 1.5mg/kg daily for 3 months improved blood glucose and insulin levels, metabolic status, and body fat in diabetic rats[7]. A single dose of GABA pretreatment (10mg/kg; i.p.) for 1 hour significantly increased the survival rate of mice with lipopolysaccharide (LPS)-induced acute lung injury (ALI), alleviated inflammatory injury and pulmonary edema, decreased the content of myeloperoxidase (MPO), down-regulated the levels of pro-inflammatory cytokines IL-1β and TNF-α, and up-regulated the expression of anti-inflammatory cytokine IL-10[8].
References:
[1] Mortensen M, Patel B, Smart T G. GABA potency at GABAA receptors found in synaptic and extrasynaptic zones[J]. Frontiers in cellular neuroscience, 2012, 6: 1.
[2] Barakat H, Aljutaily T. Role of γ-Aminobutyric acid (GABA) as an inhibitory neurotransmitter in diabetes management: mechanisms and therapeutic implications[J]. Biomolecules, 2025, 15(3): 399.
[3] Heli Z, Hongyu C, Dapeng B, et al. Recent advances of γ-aminobutyric acid: Physiological and immunity function, enrichment, and metabolic pathway[J]. Frontiers in Nutrition, 2022, 9: 1076223.
[4] Song L, Du A, Xiong Y, et al. γ-Aminobutyric acid inhibits the proliferation and increases oxaliplatin sensitivity in human colon cancer cells[J]. Tumor Biology, 2016, 37(11): 14885-14894.
[5] Untereiner A, Xu J, Bhattacharjee A, et al. γ‐aminobutyric acid stimulates β‐cell proliferation through the mTORC1/p70S6K pathway, an effect amplified by Ly49, a novel γ‐aminobutyric acid type A receptor positive allosteric modulator[J]. Diabetes, Obesity and Metabolism, 2020, 22(11): 2021-2031.
[6] Ullah A, Jahan S, Razak S, et al. Protective effects of GABA against metabolic and reproductive disturbances in letrozole induced polycystic ovarian syndrome in rats[J]. Journal of ovarian research, 2017, 10(1): 62.
[7] Sohrabipour S, Sharifi M R, Talebi A, et al. GABA dramatically improves glucose tolerance in streptozotocin-induced diabetic rats fed with high-fat diet[J]. European Journal of Pharmacology, 2018, 826: 75-84.
[8] Yang J, Li N, Zhen Y, et al. γ-aminobutyric acid alleviates LPS-induced acute lung injury in mice through upregulating type B receptors[J]. Archives of Medical Science: AMS, 2019, 19(4): 1116.
GABA是哺乳动物大脑中一种重要的内源性抑制性神经递质，对GABAA受体的α6、α1、α4和α5亚基的EC50值分别为0.17、2.1、2.1和1.4μM[1]。GABA通过囊泡抑制性氨基酸转运体被装载入突触囊泡，并调节神经元兴奋性以维持大脑功能的平衡[2]。GABA已被广泛用于不同动物模型以调节免疫反应、干扰肿瘤生长以及缓解焦虑[3]。
在体外，使用100µM的GABA处理72小时可显著抑制SW480、SW620和HCT116细胞的增殖并诱导细胞周期阻滞[4]。用100µM的GABA处理小鼠胰岛B细胞4天，能促进细胞增殖，导致p-Akt Ser473和p-p70S6K Thr421/Ser424的核内表达增加[5]。
在体内，以每日100mg/kg的剂量口服给予GABA两周，可显著改善多囊卵巢综合征（PCOs）大鼠的代谢状态，并降低体重、体重指数和睾酮水平[6]。每日腹腔注射1.5mg/kg剂量的GABA，持续3个月，改善了糖尿病大鼠的血糖和胰岛素水平、代谢状态以及体脂[7]。单次预处理GABA（10mg/kg；i.p.）1小时，可显著提高脂多糖（LPS）诱导的急性肺损伤（ALI）小鼠的存活率，减轻炎症损伤和肺水肿，降低髓过氧化物酶（MPO）含量，下调促炎细胞因子IL-1β和TNF-α的水平，并上调抗炎细胞因子IL-10的表达[8]。