• Archives of Pharmacal Research
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• 제29권5호
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• pp.400-404
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• 2006

This study examined the effect of Gamma-Amino butyric acid (GABA) and selective GABA receptor related drugs on the electrically stimulated relaxation in the lower esophageal sphincter muscle (LES) of a cat. Tetrodotoxin $(10^{-6}\;M)$ suppressed the electrically stimulated (0.5-5 Hz) relaxation of the LES. However, guanethidine $(10^{-6}\;M)$ and atropine $(10^{-6}\;M)$ had no effect indicating that the relaxations were neurally mediated via the nonadrenergic and noncholinergic (NANC) pathways. NG-nitro-L-arginine methyl ester ($10^{-4}M$, L-NAME) also inhibited the relaxant response but did not completely abolish the electrically stimulated relaxation with 60% inhibition, which suggests the involvement of nitric oxide as an inhibitory transmitter. This study examined the role of GABA, an inhibitory neurotransmitter, on neurally mediated LES relaxation. GABA ($10^{-3}-10^{-5}M$, non selective receptor agonist), muscimol ($10^{-3}-10^{-5}M$, GABA-A agonist), and baclofen ($10^{-3}-10^{-5}M$, GABA-B agonist) had no significant effect on the electrically stimulated relaxation. Moreover, bicuculline ($10^{-5}M$, GABA-A antagonist) and phaclofen ($10^{-5}M$, GABA-B antagonist) had no inhibitory effect on the electrically stimulated relaxation. This suggests that GABA and the GABA receptor are not involved in the electrically stimulated NANC relaxation in the cat LES.

• Clinical and Experimental Reproductive Medicine
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• 제48권1호
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• pp.50-60
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• 2021

Objective: This study investigated the mRNA expression of gamma-aminobutyric acid (GABA) receptors in the sperm of oligoasthenoteratozoospermic (OAT) and teratozoospermic (TER) men compared to normozoospermic (NOR) men, as well as the relationships between GABA receptor expression and sperm parameters, fertilization rate, and embryo quality. Methods: The mRNA expression of GABA A-α1 and GABA B-R2 receptors in sperm was examined using reverse transcription-polymerase chain reaction in three groups of patients: NOR (n=32), OAT (n=22), and TER (n=45). The fertilization rate and embryo quality were assessed in 35 patients undergoing intracytoplasmic sperm injection (ICSI; 10 NOR, 10 OAT, and 15 TER men). Results: OAT men had significantly higher mRNA expression of GABA A-α1 and GABA B-R2 receptors in sperm than NOR men; however, the difference between TER and NOR men was not significant. High levels of these receptors were significantly correlated with low sperm concentration, motility, and morphology, as well as the rate of good-quality embryos (GQEs) at the cleavage stage after ICSI. Patients whose female partners had a >50% GQE rate at the cleavage stage had significantly lower levels of GABA A-α1 receptor expression than those whose partners had a ≤50% GQE rate. Conclusion: Our findings indicate that mRNA levels of GABA receptors in human sperm are correlated with poor sperm quality and associated with embryo development after ICSI treatment. The GABA A-α1 receptor in sperm has a stronger relationship with embryo quality at the cleavage stage than the GABA B-R2 receptor.

• The Korean Journal of Physiology and Pharmacology
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• 제25권1호
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• pp.27-38
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• 2021

Excessive salt intake induces hypertension, but several gamma-aminobutyric acid (GABA) supplements have been shown to reduce blood pressure. GABA-salt, a fermented salt by L. brevis BJ20 containing GABA was prepared through the post-fermentation with refined salt and the fermented GABA extract. We evaluated the effect of GABA-salt on hypertension in a high salt, high cholesterol diet induced mouse model. We analyzed type 1 macrophage (M1) polarization, the expression of M1 related cytokines, GABA receptor expression, endothelial cell (EC) dysfunction, vascular smooth muscle cell (VSMC) proliferation, and medial thicknesses in mice model. GABA-salt attenuated diet-induced blood pressure increases, M1 polarization, and TNF-α and inducible nitric oxide synthase (NOS) levels in mouse aortas, and in salt treated macrophages in vitro. Furthermore, GABA-salt induced higher GABAB receptor and endothelial NOS (eNOS) and eNOS phosphorylation levels than those observed in salt treated ECs. In addition, GABA-salt attenuated EC dysfunction by decreasing the levels of adhesion molecules (E-selectin, Intercellular Adhesion Molecule-1 [ICAM-1], vascular cell adhesion molecule-1 [VCAM-1]) and of von Willebrand Factor and reduced EC death. GABA-salt also reduced diet-induced reductions in the levels of eNOS, phosphorylated eNOS, VSMC proliferation and medial thickening in mouse aortic tissues, and attenuated Endothelin-1 levels in salt treated VSMCs. In summary, GABA-salt reduced high salt, high cholesterol diet induced hypertension in our mouse model by reducing M1 polarization, EC dysfunction, and VSMC proliferation.

• 한국식품영양과학회지
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• 제46권8호
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• pp.979-985
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• 2017

본 연구는 유산균에 의한 gamma aminobutyric acid(GABA)의 생산 및 쌀겨 추출물을 이용한 최적 배지의 제조를 목표로 하고 electrostatic spray는 곡물에 GABA 함량을 증진시키기 위해 사용하였다. 분리한 Lactobacillus brevis CFM11을 MRS 배지를 이용하여 최적 조건($37^{\circ}C$, 24시간, pH 6.5)에서 배양시킨 결과, $600.12{\mu}g/mL$의 GABA 생성량을 나타냈고 0.8% MSG를 함유한 MRS 배지에서 배양시켰을 때 $2,002.93{\mu}g/mL$의 GABA 생성량을 나타냈다. 미강 추출물 배지에 MSG 0.4%, sucrose 2%, skim milk 1%, magnesium sulfate 0.2%를 첨가했을 때 GABA 생산량은 $585.80{\mu}g/mL$로 나타났다. 최적화 배지에 L. brevis CFM11을 배양시켜 얻은 GABA를 쌀 표면에 electrostatic spray 처리 후 GABA량은 $228.10{\mu}g/g$으로 나타난 반면, 아무것도 처리하지 않은 곡류에서의 GABA량은 $32.23{\mu}g/g$이었다. 이러한 결과로 보아 미강 추출물은 GABA 생산을 위한 MRS 배지의 대체물로서 산업적인 가치를 증가시킬 수 있을 것으로 판단된다.

• The Korean Journal of Physiology and Pharmacology
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• 제17권2호
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• pp.175-180
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• 2013

Resveratrol is a phytoalexin found in grapes, red wine, and berries. Resveratrol has been known to have many beneficial health effects, such as anti-cancer, neuroprotective, anti-inflammatory, and life-prolonging effects. However, relatively little is known about the effects of resveratrol on the regulation of ligand-gated ion channels. We have previously reported that resveratrol regulates subsets of homomeric ligand-gated ion channels such as those of 5-$HT_{3A}$ receptors. The ${\gamma}$-aminobutyric $acid_C$($GABA_C$) receptor is mainly expressed in retinal bipolar cells and plays an important role in visual processing. In the present study, we examined the effects of resveratrol on the channel activity of homomeric $GABA_C$ receptor expressed in Xenopus oocytes injected with cRNA encoding human $GABA_C$ ${\rho}$ subunits. Our data show that the application of GABA elicits an inward peak current ($I_{GABA}$) in oocytes that express the $GABA_C$ receptor. Resveratrol treatment had no effect on oocytes injected with $H_2O$ or with $GABA_C$ receptor cRNA. Co-treatment with resveratrol and GABA inhibited $I_{GABA}$ in oocytes with $GABA_C$ receptors. The inhibition of $I_{GABA}$ by resveratrol was in a reversible and concentration-dependent manner. The $IC_{50}$ of resveratrol was $28.9{\pm}2.8{\mu}M$ in oocytes expressing $GABA_C$ receptor. The inhibition of $I_{GABA}$ by resveratrol was in voltage-independent and non-competitive manner. These results indicate that resveratrol might regulate $GABA_C$ receptor expression and that this regulation might be one of the pharmacological actions of resveratrol on the nervous system.

• Journal of Chest Surgery
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• 제31권5호
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• pp.441-450
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• 1998

본 연구는 동맥혈압의 조절에 결정적 역할을 하는 상부연수 복외측부에 존재하는 심맥관계 활동과 관련 있는 신경세포들에 대해 iontophoresis 법으로 투여한 신경흥분전달물질의 작용기전을 규명하고자 하였다. 이를 위해서 $\alpha$-chloralose로 마취한 고양이를 실험동물로 하여 연수의 복외측부에 multibarrel 전극을 삽입하여 심맥관계 활동과 관련 있는 신경세포의 활동을 세포외기록법으로 확인한 후 세포에 iontophoresis법으로 투여한 glutamate, GABA(\ulcorner-aminobutyric acid) 및 bicuculline의 효과를 관찰하여 다음과 같은 결과를 얻었다. 1) 자발적으로 활동전압을 보이지 않는 세포에서 glutamate를 10초 주기로 5초간 iontophoresis할 때 주기적인 세포활동을 기록할 수 있었고 이 활동은 동시에 가한 GABA에 의하여 억제되었다. 2) 자발적으로 활동하고 있는 세포들에 대하여 glutamate를 투여하였을 때 활동전압의 빈도가 증가하였고 GABA에 의해서 억제되었다. 3) GABA억제제인 bicuculline을 단독으로 투여시 활동전압 빈도의 증가는 뚜렷하지 않았으나 GABA와 동시 투여시에는 GABA의 억제작용을 차단하였다. 4) GABA의 작용은 RVLM(rostral ventrolateral medulla) 세포의 주기적 활동과 basal discharge 모두를 감소시켰으나 주기적 양상이 없어진 세포는 드물었다. 5) 말초에 가한 유해자극에 의하여 유발된 신경세포 활동이 GABA에 의하여 억제되었다. 이상의 결과로부터 $\alpha$-chloralose로 마취한 고양이에서 GABA는 RVLM에 존재하는 심맥관계 신경세포들에 대하여 억제적으로 작용하나 bicuculline의 투여후에도 이들 세포들의 주기적 활동이 유지되는 점으로 보아 RVLM세포의 자발적 흥분에 대하여 감압반사의 흥분이 기여하는 바가 크지는 않을 것으로 사료된다.

• 한국해양바이오학회지
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• 제10권1호
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• pp.18-25
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• 2018

Chlorella is quantitatively and qualitatively high in protein with balanced essential amino acid profiles, vitamins and minerals. ${\gamma}-Aminobutyric$ acid (GABA) is broadly distributed in nature and fulfills multi-physiological functions including effect such as a health-promoting functional compound. To improve the GABA production, Chlorella protothecoides were grown through the modified mixtrophic culture medium containing 2L of sterilized bristol medium with 0.01% urea and 4.0% glucose in a 5L fermenter. The results showed that nineteen kinds of amino acid including GABA at C. protothecoides sample were analyzed using high performance liquid chromatography (HPLC). Glutamic acid in total concentration (%) of amino acid is the most abundant amino acid (33.10%), followed by alanine (20.48%) and GABA (17.48%). Three amino acids including GABA were responsible for more than 70% total concentration in C. protothecoides sample including eight essential and nine non-essential amino acids: aspartic acid, asparagine, serine, glutamine, histidine, glycine, threonine, arginine, tyrosine, valine, methionine, tryptophan, phenylalanine, isoleucine, leucine, lysine. As a result of this experiment, it is expected that Chlorella will be developed to a critical product having high value as, GABA, functional food materials.

• The Korean Journal of Physiology and Pharmacology
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• 제3권5호
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• pp.461-469
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• 1999

Glutamate and ${\gamma}-aminobutyric$ acid (GABA) are major excitatory and inhibitory neurotransmitters in the vertebrate retina, respectively. Using the whole-cell patch clamp technique and a rapid solution changer, glutamate and GABA receptors have been extensively investigated in carp retina. Glutamate receptors on both horizontal and amacrine cells may be an AMPA preferring subtype, which predominantly consists of flop splice variants. $GABA_A$ and $GABA_C$ receptors coexist in bipolar cells and they both show significant desensitization. Kinetics analysis demonstrated that activation, deactivation and desensitization of the $GABA_C$ receptor-mediated response of these cells are overall slower than those of the $GABA_A$ response. Endogenous modulator $Zn^{2+}$ in the retina was found to differentially modulate the kinetic characteristics of the $GABA_C$ and $GABA_A$ responses.

• Journal of Microbiology and Biotechnology
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• 제16권4호
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• pp.562-568
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• 2006

GABA $(\gamma-aminobutyric\;acid)$ is the principal inhibitory neurotransmitter in the brain. For the efficient production of GAB A, a semi continuous cell entrapment system using Lactobacillus brevis GABA 057 was optimized, including the substrate concentration, bead-stabilizing additives, and reaction conditions. The converted monosodium glutamate (MSG), which was added as a substrate for glutamic acid decarboxylase (GAD), increased from 2% (w/v) to 12% (w/v). The addition of isomaltooligosaccharide to the alginate beads also increased the stability of the entrapped L. brevis and GABA productivity. Consequently, when optimal conditions were applied, up to 223 mM GABA could be produced from 534 mM MSG after 48 h of reaction by using alginate-beadencapsulated L. brevis GABA 057.

• Journal of Microbiology and Biotechnology
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• 제27권9호
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• pp.1664-1669
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• 2017

Gamma-aminobutyric acid is a precursor of nylon-4, which is a promising heat-resistant biopolymer. GABA can be produced from the decarboxylation of glutamate by glutamate decarboxylase. In this study, a synthetic scaffold complex strategy was employed involving the Neurospora crassa glutamate decarboxylase (GadB) and Escherichia coli GABA antiporter (GadC) to improve GABA production. To construct the complex, the SH3 domain was attached to the N. crassa GadB, and the SH3 ligand was attached to the N-terminus, middle, and C-terminus of E. coli GadC. In the C-terminus model, 5.8 g/l of GABA concentration was obtained from 10 g/l glutamate. When a competing pathway engineered strain was used, the final GABA concentration was further increased to 5.94 g/l, which corresponds to 97.5% of GABA yield. With the introduction of the scaffold complex, the GABA productivity increased by 2.9 folds during the initial culture period.