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.