• Anxiety and mood
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• v.2 no.2
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• pp.79-85
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• 2006

Anxiety and anxiety disorders are related to many neurotransmitters, such as norepinephrine, serotonine, dopamine, glutamate, and Gamma-aminobutyric acid (GABA). GABA, the main inhibitory neurotransmitter of the CNS, is known to counterbalance the action of the excitatory neurotransmitters and control anxiety. GABA acts on 3 GABA receptor subtypes, $GABA_A$, $GABA_B$, and $GABA_C$. $GABA_A$ and $GABA_c$ receptors are oligomeric transmembrane glycoproteins composed of 5 subunits that are arranged around a central chloride channel. $GABA_B$ receptor comprises two 7-transmembraneis-spanning proteins that are coupled to either calcium or potassium channel via G proteins. This article highlights neurobiological interactions between anxiety and GABA system.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.6
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• pp.721-729
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• 2018

GABAergic control over dopamine (DA) neurons in the substantia nigra is crucial for determining firing rates and patterns. Although GABA activates both $GABA_A$ and $GABA_B$ receptors distributed throughout the somatodendritic tree, it is currently unclear how regional GABA receptors in the soma and dendritic compartments regulate spontaneous firing. Therefore, the objective of this study was to determine actions of regional GABA receptors on spontaneous firing in acutely dissociated DA neurons from the rat using patch-clamp and local GABA-uncaging techniques. Agonists and antagonists experiments showed that activation of either $GABA_A$ receptors or $GABA_B$ receptors in DA neurons is enough to completely abolish spontaneous firing. Local GABA-uncaging along the somatodendritic tree revealed that activation of regional GABA receptors limited within the soma, proximal, or distal dendritic region, can completely suppress spontaneous firing. However, activation of either $GABA_A$ or $GABA_B$ receptor equally suppressed spontaneous firing in the soma, whereas $GABA_B$ receptor inhibited spontaneous firing more strongly than $GABA_A$ receptor in the proximal and distal dendrites. These regional differences of GABA signals between the soma and dendritic compartments could contribute to our understanding of many diverse and complex actions of GABA in midbrain DA neurons.

• Biomedical Science Letters
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• v.12 no.2
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• pp.113-118
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• 2006

Major pelvic ganglia (MPG) in rats are an unique autonomic ganglia, containing both sympathetic and parasympathetic neurons related with the function of bladder, penis and bowel. It has been widely known that ionotropic $GABA_A$ receptors are the molecular target of $\gamma$-aminobutric acid (GABA), a major inhibitory neurotransmitter in central nervous system. However, their functions and regulations of $GABA_A$ receptors expressed in autonomic ganglia have been poorly understood. 1 examined the modulatory role of adenylyl cyclase (AC) and protein kinase A(PKA) on $GABA_A$-induced inward currents in the neurons of rat MPG. $GABA_A$ receptors were identified using immunofluorescent labeling in the rat major pelvic ganglion. Electrophysiological experiments were performed to record the activities of $GABA_A$ receptors. $GABA_A$ receptors were expressed only in sympathetic neurons. GABA induced marked inward currents in a concentration-dependent manner. Mucimol ($5{\mu}M$), a $GABA_A$ receptor agonist induced inward currents were significantly reduced in the presence of SQ 225361 $20{\mu}M$, a AC inhibitor and myristoylated PKA inhibitor 100 nM. In addition, forskolin ($1{\mu}M$), AC activator, augmented the GABA induced currents. The activation of AC/PKA-dependent pathway could involve in the regulation $GABA_A$ receptors, expressed only in sympathetic neurons of rat MPG. These findings are helpful for the better understanding the function of various pelvic organs innervated by MPG.

• Nuclear Medicine and Molecular Imaging
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• v.41 no.2
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• pp.166-171
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• 2007

GABA is primary an inhibitory neurotransmitter that is localized in inhibitory interneurons. GABA is released from presynaptic terminals and functions by binding to GABA receptors. There are two types of GABA receptors, $GABA_{A}-receptor$ that allows chloride to pass through a ligand gated ion channel and $GABA_{B}-receptor$ that uses G-proteins for signaling. The $GABA_{A}$-receptor has a GABA binding site as well as a benzodiazepine binding sites, which modulate $GABA_{A}$-receptor function. Benzodiazepine GABAA receptor imaging can be accomplished by radiolabeling derivates that activates benzodiazepine binding sites. There has been much research on flumazenil (FMZ) labeled with $^{11}C-FMZ$, a benzodiazepine derivate that is a selective, reversible antagonist to GABAA receptors. Recently, $^{18}F-fluoroflumazenil$ (FFMZ) has been developed to overcome $^{11}C's$ short half-life. $^{18}F-FFMZ$ shows high selective affinity and good pharmacodynamics, and is a promising PET agent with better central benzodiazepine receptor imaging capabilities. In an epileptic focus, because the GABA/benzodiazepine receptor amount is decreased, using $^{11}C-FMZ$ PET instead of $^{18}F-FDG$ PET, restrict the foci better and may also help find lesions better than high resolution MR. $GABA_{A}$ receptors are widely distributed in the cerebral cortex, and can be used as an viable neuronal marker. Therefore it can be used as a neuronal cell viability marker in cerebral ischemia. Also, GABA-receptors decrease in areas where neuronal plasticity develops, therefore, $GAB_{A}$ imaging can be used to evaluate plasticity. Besides these usages, GABA receptors are related with psychological diseases, especially depression and schizophrenia as well as cerebral palsy, a motor-related disorder, so further in-depth studies are needed for these areas.

• Journal of Yeungnam Medical Science
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• v.8 no.2
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• pp.95-105
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• 1991

This study was designed to investigate the effect of GABA and related substances on the spontaneous contraction of rat small intestine. The rats(Sprague-Dawley), weighing 200-250g, were sacrificed by cervical dislocation, and the small intestine was isolated. Longitudinal muscle strips from duodenum, jejunum and ileum were suspended in Biancani's isolated muscle chambers and myographied isometrically. GABA and muscimol, a GABA A receptor agonist relaxed the duodenum and jejunum significantly, but baclofen-induced relaxation in those muscle strips was negligible. The effectiveness of GABA and muscimol in various regions were the greatest on duodenum, and greater on jejunum than on ileum The effect of GABA and muscimol was antagonized by bicuculline, a compeptitive GABA A receptor antagonist and picrotoxin, a noncomptitive GABA A receptor antagonist. Duodenal relaxation induced by GABA and muscimol was unaffected by hexamethonium, but was prevented by tetrodotoxin. These results suggest that GABA inhibit the contractility of smooth muscle with distinct regional difference of efficacy, and the site of inhibitory action is the GABA A receptor existing at the presynaptic membrane of postganglionic excitatory nerves.

• KOREAN JOURNAL OF CROP SCIENCE
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• v.57 no.2
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• pp.144-150
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• 2012

${\gamma}$-Aminobutyric acid (GABA) is a non-protein amino acid that is widely distributed in plant and animal kingdom. GABA is found in tissues of the central nervous system (CNS) in animals. GABA functions as a the major inhibitory neurotransmitter in the CNS by acting through the GABA receptors. Clinical studies have revealed the relationship between an increased intake of GABA or analogues with several health benefits, including lowering of blood pressure in mildly hypertensive animals and humans. Furthermore, GABA would also has an inhibitory effect on cancer cell proliferation, stimulates cancer cell apoptosis and plays a role in alcohol-associated diseases and schizophrenia. In plants, interest in the GABA emerged mainly from experimental observations that GABA is largely and rapidly produced in large amounts in response to biotic and abiotic stresses. In this study, we speculated the properties and metabolism of GABA in plant and functions in relation to the responses to environmental stresses.

• Journal of Yeungnam Medical Science
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• v.11 no.2
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• pp.314-322
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• 1994

This study aimed to investigate the existence of GABA receptor and the mechanisms of action of GABA and diazepam on the trachealis muscle isolated from dog. Horizontal muscle strips of $2mm{\times}15mm$ were prepared from canine trachea, and isometric myography in isolated muscle chamber bubbled with 95/5%-$O_2/CO_2$at $36^{\circ}C$, at the pH of 7.4 was performed. Muscle strips contracted responding to the electrical field stimulation (ESP) by 2~20 Hz, 20 msec, monophasic square wave of 60 VDC GABA and diazepam suppressed the EFS-induced contractions to the similar extent, significantly. (p<0.05) Bicuculline, a $GABA_A$ receptor antagonist blocked both GABA- and diazepam- inhibitions; but DAVA, a $GABA_B$ receptor antagonist did not affect either of them. These results suggest that in the canine trachealis muscle, there may be only $GABA_A$ receptor, and GABA and diazepam inhibit the contractility via $GABA_A$A receptor.

• YAKHAK HOEJI
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• v.36 no.5
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• pp.496-505
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• 1992

The correlation between GABA receptors($GABA_A$ and $GABA_B$ receptor) and benzodiazepine receptor on the saline infusion-induced micturition reflex contraction was studied in the female rat. To investigate the effect of ${\gamma}-aminobutyric$ acid(GABA) on the micturition reflex, exogenous GABA(10 mg/kg) and GABA transaminase inhibitor(aminooxyacetic acid; AOAA $1\;{\mu}g$) were administered intravenously(i.v.) and intracerebroventriculary(i.c.v.), respectively. In result, both GABA and AOAA inhibited the saline induced micturition reflex contraction. This AOAA induced inhibition of micturition reflex was blocked by both bicuculine. $GABA_A$ receptor antagonist, and Ro 15-1788, benzodiazepine receptor antagonist. Muscimol, $GABA_A$ receptor antagonist($0.1\;{\mu}g$ i.c.v., $3\;{\mu}g$ intrathecal; i.t., 1 mg/kg i.v.) and baclofen, $GABA_A$ receptor agonist($1\;{\mu}g$ i.c.v., $3\;{\mu}g$ i.t., 1 mg/kg i.v.) also inhibited the bladder contraction. Pretreatment of bicuculline($1\;{\mu}g$ i.c.v.), but not of 5-aminovaleric acid(AVA, $1\;{\mu}g$ i.c.v.), $GABA_B$ receptor antagonist blocked the central inhibition of muscimol. These inhibitory effects were reversed by Ro15-1788 but were potentiated by flurazepam, benzodiazepine receptor antagonist. On the other hand, the inhibitory effects of baclofen were not affected by Ro 15-1788. Diazepam and flurazepam also inhibited the micturition reflex contraction when they were administered $3\;{\mu}g$ i.c.v., $10\;{\mu}g$ i.t., $10\;{\mu}M$, $30\;{\mu}M$ transurethrally, respectively. In conclusion, these results suggest that the micturition reflex is mediated by $GABA_A$, $GABA_B$ receptor and benzodiazepine receptor. The bezodiazepines increase the receptor binding of GABA to the $GABA_A$ receptor, so that the benzodiiazepines show the synergistic effect on the inhibition of the micturition reflex contraction, but not to the $GABA_B$ receptor.

• Journal of Yeungnam Medical Science
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• v.9 no.2
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• pp.382-395
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• 1992

GABA is an inhibitory neurotransmitter in central nervous system and produce sedative, antianxiety and muscle reaxing effects via $GABA_A$ receptor or $GABA_B$ receptor. Recently it is known that GABA is widely distributed throughout peripheral organs and may playa physiological role in certain organ. The vas deferens is innervated by species-difference. These study, therefore, was performed to investigate the mode and the mechanism of action of GABA on the norepiniphrine-, ATP- and electric stimulation-induced contraction of vas deferens of rat. Sprague-Dawley rats were sacrificed by cervical dislocation. The smooth muscle strips were isolated from the prostastic portion and were mounted in the isolated muscle bath. PSS in the bath was aerated with 95/5%-$O_2/CO_2$ at $33^{\circ}C$. Muscle tensions were measured by isometric tension transducer and were recorded by biological recording system. 1. GABA, muscimol, a $GAB_A$ agonist, and baclofen, a $GABA_B$ agonist inhibited the electric field stimulation(EFS, 0.2Hz, 1mSec, 80 V, monophasic square wave)-induced contraction with a rank order of potency of GABA greater than baclofen greater than muscimol. 2. The inhibitory effect of GABA was antagonized by delta aminovaleric acid(DAVA), a $GABA_B$ antagonist, but not by bicuculline, a $GABA_A$ mtagonist. 3. The inhibitory effect of baclofen was antagonized by DAVA, but the effect of muscimol was not antagonized by bicuculline. 4. Exogenous norepinephrine(NE) and ATP contracted muscle strip concentration dependently, but the effect of acetylcholine was negligible : and GABA did not affect the NE-and ATP-induced contractions. 5. GABA, baclofen and muscimol did not affect basal tone, and GABA did not affect the NE-and ATP-induced contractionsm 6. EFS-induced contraction was including 2 distinctable components. The first phasic component was inhibited by beta gamma-methylene ATP(mATP), a desensitizing agent of APT receptor and the second tonic component was reduced by pretreatment of reserpine(3 mg/Kg, IP). 7. GABA inhibited the EFS-induced contraction of reserpinized strips, but not the mATP-treated strips. These results suggest that in the prostatic portion of the rat vas deferens, adrenergic and purinergic neurotransmissions are exist, and GABA inhibits the release of ATP via presynaptic $GABA_B$ receptor on the excitatory neurons.

• Journal of Microbiology and Biotechnology
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• v.26 no.4
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• pp.710-716
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• 2016

Gamma-aminobutyric acid (GABA) is a non-protein amino acid, which is an important inhibitor of neurotransmission in the human brain. GABA is also used as the precursor of biopolymer Nylon-4 production. In this study, the carbon flux from the tricarboxylic acid cycle was directed to the GABA shunt pathway for the production of GABA from glucose. The GABA shunt enzymes succinate-semialdehyde dehydrogenase (GabD) and GABA aminotransferase (GabT) were co-localized along with the GABA transporter (GadC) by using a synthetic scaffold complex. The co-localized enzyme scaffold complex produced 0.71 g/l of GABA from 10 g/l of glucose. Inactivation of competing metabolic pathways in mutant E. coli strains XBM1 and XBM6 increased GABA production 13% to reach 0.80 g/l GABA by the enzymes co-localized and expressed in the mutant strains. The recombinant E. coli system developed in this study demonstrated the possibility of the pathway of the GABA shunt as a novel GABA production pathway.