• The Korean Journal of Pain
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• 제19권1호
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• pp.22-32
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• 2006

Background: This study was conducted to investigate the roles of the spinal and peripheral ${\gamma}$-aminobutyric acid (GABA)- ergic systems for the mechanical hypersensitivity produced by chronic compression of the dorsal root ganglion (CCD). Methods: CCD was performed at the left 5th lumbar dorsal root ganglion. The paw withdrawal threshold (PWT) to von Frey stimuli was measured. The mechanical responsiveness of the lumbar dorsal horn neurons was examined. GABAergic drugs were delivered with intrathecal (i.t.) or intraplantar (i.pl.) injection or by topical application onto the spinal cord. Results: CCD produced mechanical hypersensitivity, which was evidenced by the decrease of the PWT, and it lasting for 10 weeks. For the rats showing mechanical hypersensitivity, the mechanical responsiveness of the lumbar dorsal horn neurons was enhanced. A similar increase was observed with the normal lumbar dorsal horn neurons when the GABA-A receptor antagonist bicuculline was topically applied. An i.t. injection of GABA-A or GABA-B receptor agonist, muscimol or baclofen, alleviated the CCD-induced hypersensitivity. Topical application of same drugs attenuated the CCD-induced enhanced mechanical responsiveness of the lumbar dorsal horn neurons. CCD-induced hypersensitivity was also improved by low-dose muscimol applied (i.pl.) into the affected hind paw, whereas no effects could be observed with high-dose muscimol or baclofen. Conclusions: The results suggest that the neuropathic pain associated with compression of the dorsal root ganglion is caused by hyperexcitability of the dorsal horn neurons due to a loss of spinal GABAergic inhibition. Peripheral application of low-dose GABA-A receptor agonist can be useful to treat this pain.

• 한국동물학회지
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• 제33권2호
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• pp.133-140
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• 1990

한 눈의 시각에서 bead와 눈의 optokinetic nystagmus(OKN)은 닭과 같은 하등 척추동물에서 반사 시각운동을 일으키는데 temporal-nasal(T-N)자극이 nasal-temporal(N-T)자극보다 더욱 효과적인 방향적 불균형성을 나타낸다. 닭의 한쪽 눈 봉합에 의한 장기간 한쪽 눈 시각상실은 N-T성분이 점진적으로 많은 증가를 일으킨다는 것을 코일에 의한 기록과 관찰에서 보여주었다. 이 plasticity현상은 닭에서 눈과 head OKN에 관련되고 있다. GABA agonist인 5,6,7-tetrahydroisoxzolo(5,4,C)pyridin-3-10(THIP)주입은 닭에서 NT성분의 증가를 가역적으로 제거하였다. 이 사실은 GABAergic시스템이 성장한 하등 척축동물에서 관찰된 이 plasticity현상을 결정하는데 관련될 수 있다는 것을 시사하고 있다.

• Biomolecules & Therapeutics
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• 제23권3호
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• pp.268-274
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• 2015

${\gamma}$-Aminobutyric acid (GABA), a major inhibitory neurotransmitter in the mammalian central nervous system, is involved in sleep physiology. Caffeine is widely used psychoactive substance known to induce wakefulness and insomnia to its consumers. This study was performed to examine whether GABA extracts from fermented rice germ ameliorates caffeine-induced sleep disturbance in mice, without affecting spontaneous locomotor activity and motor coordination. Indeed, caffeine (10 mg/kg, i.p.) delayed sleep onset and reduced sleep duration of mice. Conversely, rice germ ferment extracts-GABA treatment (10, 30, or 100 mg/kg, p.o.), especially at 100 mg/kg, normalized the sleep disturbance induced by caffeine. In locomotor tests, rice germ ferment extracts-GABA slightly but not significantly reduced the caffeine-induced increase in locomotor activity without affecting motor coordination. Additionally, rice germ ferment extracts-GABA per se did not affect the spontaneous locomotor activity and motor coordination of mice. In conclusion, rice germ ferment extracts-GABA supplementation can counter the sleep disturbance induced by caffeine, without affecting the general locomotor activities of mice.

• Preventive Nutrition and Food Science
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• 제8권2호
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• pp.119-123
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• 2003

To investigate the effects of the supplementation of carnitine and/or ${\gamma}$ -aminobutric acid (GABA), Sprague-Dawley male rats were orally treated with either an AIN-76 diet (control), a control diet plus ethanol (CE, 4 g ethanol/kg bw), CE plus L-carnitine (CEC, 0.5 g/kg bw), CE plus GABA (CEG, 0.5 g/kg bw), or CE plus L-carnitine plus GABA (CECG, 0.25 g/kg bw each) for 6 weeks. Serum triglyceride levels were increased in the CE group and were decreased significantly in the CEC, CEG and CECG groups. HDL-cholesterol was increased and LDL-cholesterol was decreased in the CEG and CECG groups compared with the CE group. Serum GOT and GPT levels increased by the chronic ethanol administration were decreased in the CEC group. In addition, we have evaluated the mRNA levels of carnitine palmitoyltransferase-I in those groups. Supplementation of carnitine/GABA had some recovery effects on the liver CPT-I mRNA levels which decreased by chronic ethanol administration. These results may suggest that supplementations of either L-carnitine or GABA aye effective on the recovery of chronic ethanol-related symptoms, but no combined effects were shown.

• Journal of Ginseng Research
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• 제14권2호
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• pp.213-216
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• 1990

• 생명과학회지
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• 제30권3호
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• pp.260-266
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• 2020

알코올 중독과 GABA계와의 관련성에 대한 많은 연구가 있으며, 중추신경계의 GABA계를 항진시키면 알코올 중독의 재발을 억제한다는 보고가 있다. 이에 GABA 고함유쌀과 저함유쌀의 섭취가 생쥐의 알코올 섭취 행동에 미치는 영향을 조사하고자 한다. 흑찰거대배아미(BSRGE), 조생흑찰벼(BSR)와 거대배아미(GER) 및 일반미(Rice)를 각각 현미상태에서 48시간 발아시켜 배아만을 채취하여 발아현미배아의 비율이 70%가 함유되도록 기존의 사료에 혼합하여 사료화한 후 C57BL/6 생쥐에게 16일 동안 자유 섭취시키면서 2시간 알코올 섭취량, 22시간 물 섭취량, 24시간 사료섭취량 및 체중의 변화를 조사하였다. 흑찰거대배아미군과 조생흑찰군 간에 일별 2시간 알코올 섭취량의 일변화에 대해 repeated measure ANOVA를 실시하였을 때에 섭취일수(시간)에 따라서는 유의한 차이가 나타났다(df=7, F=4.812, p=0.026). 일별 2시간 알코올 섭취량의 일변화에 대해 양군을 비교하였을 때, BSR에 비하여 BSRGE에서 2시간 알코올 섭취량이 유의하게 감소하였으며, 이러한 감소효과는 섭취 10일째부터 16일째까지 지속적으로 나타났다(10일째, df=14, t=3.18, p=0.012; 12일째, df=14, t=3.39, p=0.004; 14일째, df=14, t=5.11, p=0.001; 16일째, df=14, t=6.79, p<0.001). GER과 Rice 양군을 비교하였을 때 Rice에 비하여 GER에서 2시간 알코올 섭취량이 유의하게 감소하였으며, 이러한 감소효과는 섭취 12일째부터 16일째까지 지속적으로 나타났다(12일째, df=14, t=2.61, p=0.021; 14일째, df=14, t=4.24, p=0.001; 16일째, df=14, t=2.81, p=0.023). GABA 고함유쌀인 BSRGE과 GER을 첨가한 사료를 섭취한 경우 GABA 저함유쌀인 BSR과 Rice를 첨가한 사료를 섭취한 것에 비해 C57BL/6 생쥐의 알코올 섭취량이 억제되었다. 이는 GABA 고함유쌀인 흑찰거대배아미가 알코올 사용 장애 환자의 재발 방지에 시도될 수 있음을 시사하고 있다.

• Journal of Microbiology and Biotechnology
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• 제17권10호
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• pp.1661-1669
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• 2007

Gamma-aminobutyric acid (GABA) is a non-protein amino acid. It is well known for its role as an inhibitory neurotransmitter of developing and operating nervous systems in brains. In this study, a novel function of GABA in the healing process of cutaneous wounds was presented regarding anti-inflammation and fibroblast cell proliferation. The cell proliferation activity of GABA was verified through an MTT assay using murine fibroblast NIH3T3 cells. It was observed that GABA significantly inhibited the mRNA expression of iNOS, IL-$1{\beta}$, and TNF-${\alpha}$ in LPS-stimulated RAW 264.7 cells. To evaluate in vivo activity of GABA in wound healing, excisional open wounds were made on the dorsal sides of Sprague-Dawley rats under anesthesia, and the healing of the wounds was apparently assessed. The molecular aspects of the healing process were also investigated by hematoxylineosin staining of the healed skin, displaying the degrees of re-epithelialization and linear alignment of the granulation tissue, and immunostaining and RT-PCR analyses of fibroblast growth factor and platelet-derived growth factor, implying extracellular matrix synthesis and remodeling of the skin. The GABA treatment was effective to accelerate the healing process by suppressing inflammation and stimulating re-epithelialization, compared with the epidermal growth factor treatment. The healing effect of GABA was remarkable at the early stage of wound healing, which resulted in significant reduction of the whole healing period.

• Journal of Applied Biological Chemistry
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• 제56권2호
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• pp.89-93
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• 2013

Gamma-aminobutyric acid (GABA) aminotransferase (gabT) and succinic semialdehyde dehydrogenase (gabD) genes from Pseudomonas fluorescens KCCM 12537 were cloned into a single pETDuet-1 vector and co-expressed in Escherichia coli BL21(DE3) simultaneously. The mixture of both enzymes, called GABase, is the key enzyme for the enzymatic analysis of GABA. The molecular mass of the GABA aminotransferase and succinic semialdehyde dehydrogenase were determined to be 52.8 and 46.7 kDa following computations performed with the pI/Mw program, respectively. The GABase activity between pH 6.0 and 9.0 for 24 h at $4^{\circ}C$ remained over 75%, but under pH 6.0 decreased rapidly. The GABase activity between 25 and $35^{\circ}C$ by the treatment at pH 8.6 for 30 min remained over 80%, but over $35^{\circ}C$ decreased rapidly. When the activity against GABA was defined as 100%, the purified GABase activity against 5-aminovaleric acid having a similar structure to GABA showed 47.7% and GABase activity against ${\beta}$-alanine, ${\varepsilon}$-amino-n-caproic acid, $_L$-ornithine, $_L$-lysine, and $_L$-aspartic acid showed between 0.3 to 2.3%. The GABA content was analyzed with this co-expressed GABase, compared with the other GABase which was available commercially. As a result, the content of GABA extracted from brown rice, dark brown rice, and black rice were $26.4{\pm}3.5$, $40.5{\pm}4.7$ and $94.7{\pm}9.3{\mu}g/g$, which were similar data of other GABase in the error ranges.

• 동의신경정신과학회지
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• 제19권1호
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• pp.43-54
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• 2008

Objective: The aim of this study is to evaluate the anticonvulsive effects of Gamiheichumhwan extract and to explain its action in GABAergic neuromodulation of the rat brain. Method: The extracts of Gamiheichumhwan were investigated for their inhibitory effect on GABA transaminase activity, their influence on brain GABA and glutamate levels, their agonistic activity on GABA/benzodiazepine receptor and anticonvulsive action using in vitro and in vivo assays. Results: 1. The extract inhibited dose-dependently GABA transaminase (GABA-T) activity by 4.6% and 18.9%, respectively at dosages of 250 mg/kg and 500mg/kg mouse (p.o.). 2. Brian GABA level was increased to 72.0% and brain glutamate level was decreased to 9.6% at a dosage of 500 mg/kg mouse (p.o.). 3. The extract suppressed [3H]Ro15-1788 binding to rat cerebral cortical membrane by $81.4{\pm}0.8%$ at a dosage of 3.2 mg, suggesting its agonistic activity on GABA/benzodiazepin receptor. 4. The extract showed anticonvulsive effect by lengthening the onset time of convulsion, shortening the convulsion duration and diminishing the lethality. Conclusion : It is suggested that Gamiheichumhwan can be used to somnipathy and adapted to treatment and prevention of epilepsy or convulsion.

• Asian Pacific Journal of Cancer Prevention
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• 제15권2호
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• pp.1041-1046
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• 2014

Evidence is growing that the $GABA_B$ receptor, which belongs to the G protein-coupled receptor (GPCR) superfamily, is involved in tumorigenesis. Recent studies have shown that ${\beta}$-arrestin can serve as a scaffold to recruit signaling protein c-Jun N-terminal knase (JNK) to GPCR. Here we investigated whether ${\beta}$-arrestin recruits JNK to the $GABA_B$ receptor and facilitates its activation to affect the growth of cancer cells. Our results showed that ${\beta}$-arrestin expression is decreased in breast cancer cells in comparison with controls. ${\beta}$-arrestin could enhance interactions of the $GABA_BR{\cdot}{\beta}-arrestin{\cdot}JNK$ signaling module in MCF-7 and T-47D cells. Further studies revealed that increased expression of ${\beta}$-arrestin enhances the phosphorylation of JNK and induces cancer cells apoptosis. Collectively, these results indicate that ${\beta}$-arrestin promotes JNK mediated apoptosis via a $GABA_BR{\cdot}{\beta}-arrestin{\cdot}JNK$ signaling module.