No abstract available.
Amines ; Cyclohexanecarboxylic Acids ; gamma-Aminobutyric Acid ; Hiccup

No abstract available.
gamma-Aminobutyric Acid* ; Nervous System* ; Receptors, GABA*

No abstract available.
Benzodiazepines* ; gamma-Aminobutyric Acid* ; Receptors, GABA-A*

No abstract available.
Adenosine Triphosphatases* ; Animals ; Brain* ; gamma-Aminobutyric Acid* ; Phenytoin* ; Rats*

A rapid, sensitive and convenient LC-MS/MS method was developed for the determination of γ-aminobutyric acid (GABA) in human plasma. d2-γ-Aminobutyric acid (d2-GABA) was synthesized as internal standard (IS). After extraction from human plasma by protein precipitation with acetonitrile, all analytes were separated on a Luna HILIC column (100 mm x 3.0 mm, 3 μm) using an isocratic mobile phase of water: acetonitrile: formic acid (20 : 80 : 0.12) with a flow rate of 0.5 mL x min(-1). Acquisition of mass spectrometric data was performed in multiple reaction monitoring mode (MRM) in positive electrospray ionization using the transitions of m/z 104 --> 69 for GABA and m/z 106 --> 71 for d2-GABA. The method was linear in the concentration range of 5.00 to 1 000 ng x mL(-1). The intra- and inter-day precisions were within 9.9%, and accuracy ranged from 99.1% to 104%, within the acceptable limit across all concentrations. The method was successfully applied to a pharmacokinetic study of GABA tablets in healthy Chinese volunteers.
Chromatography, Liquid ; Humans ; Tandem Mass Spectrometry ; gamma-Aminobutyric Acid ; blood

This study was done to produce γ-aminobutyric acid (GABA) from wild yeast as well as investigate its anti-hyperglycemic effects. Among ten GABA-producing yeast strains, Pichia silvicola UL6-1 and Sporobolomyces carnicolor 402-JB-1 produced high GABA concentration of 134.4 µg/mL and 179.2 µg/mL, respectively. P. silvicola UL6-1 showed a maximum GABA yield of 136.5 µg/mL and 200.8 µg/mL from S. carnicolor 402-JB-1 when they were cultured for 30 hr at 30℃ in yeast extract-peptone-dextrose medium. The cell-free extract from P. silvicola UL6-1 and S. carnicolor 402-JB-1 showed very high anti-hyperglycemic α-glucosidase inhibitory activity of 72.3% and 69.9%, respectively. Additionally, their cell-free extract-containing GABA showed the anti-hyperglycemic effect in streptozotocin-induced diabetic Sprague-Dawley rats.
gamma-Aminobutyric Acid ; Pichia* ; Rats, Sprague-Dawley ; Yeasts*

5-Hydroxytryptamine (5-HT) type 3 receptor (5-HT₃R) is the only type of ligand-gated ion channel in the 5-HT receptor family. Through the high permeability of Na⁺, K⁺, and Ca²⁺ and activation of subsequent voltage-gated calcium channels (VGCCs), 5-HT₃R induces a rapid increase of neuronal excitability or the release of neurotransmitters from axon terminals in the central nervous system (CNS). 5-HT₃Rs are widely expressed in the medial prefrontal cortex (mPFC), amygdala (AMYG), hippocampus (HIP), periaqueductal gray (PAG), and other brain regions closely associated with anxiety reactions. They have a bidirectional regulatory effect on anxiety reactions by acting on different types of cells in different brain regions. 5-HT₃Rs mediate the activation of the cholecystokinin (CCK) system in the AMYG, and the γ‍-aminobutyric acid (GABA) "disinhibition" mechanism in the prelimbic area of the mPFC promotes anxiety by the activation of GABAergic intermediate inhibitory neurons (IINs). In contrast, a 5-HT₃R-induced GABA "disinhibition" mechanism in the infralimbic area of the mPFC and the ventral HIP produces anxiolytic effects. 5-HT₂R-mediated regulation of anxiety reactions are also activated by 5-HT₃R-activated 5-HT release in the HIP and PAG. This provides a theoretical basis for the treatment of anxiety disorders or the production of anxiolytic drugs by targeting 5-HT₃Rs. However, given the circuit specific modulation of 5-HT₃Rs on emotion, systemic use of 5-HT₃R agonism or antagonism alone seems unlikely to remedy anxiety, which deeply hinders the current clinical application of 5-HT₃R drugs. Therefore, the exploitation of circuit targeting methods or a combined drug strategy might be a useful developmental approach in the future.
Serotonin ; Receptors, Serotonin, 5-HT3 ; Anxiety ; Neurons ; gamma-Aminobutyric Acid

Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter in the adult central nervous system (CNS), however, it causes excitation in the immature CNS neurons. The shift from GABA-induced depolarization to hyperpolarization in postnatal brain is primarily due to progressive decrease in the expression of the Na-K-2Cl symporter 1 (NKCC1) and increased expression of the K-Cl cotransporter 2 (KCC2). Unlike CNS neurons, both immature and mature neurons in the enteric nervous system (ENS) are depolarized by GABA. Molecular mechanisms by which GABA excites ENS neurons are unclear. It is understood, however, that the excitatory action depends on elevated intraneuronal Cl. We aimed to test a hypothesis that high intracellular Cl in ENS neurons is maintained by activity of the NKCCs. We found that NKCC2 immunoreactivity (IR) was expressed in the ENS of the rat colon on postnatal day 1 (P1). The expression level of NKCC2 continuously increased and reached a steady high level on P14 and maintained at that level in adulthood. NKCC1 IR appeared in ENS on P14 and maintained through adulthood. KCC2 IR was not detectable in the ENS in any of the developmental stages. Both NKCC1 IR and NKCC2 IR were co-expressed with GABA receptors in ENS neurons. Exogenous GABA (1 mmol/L) caused membrane depolarization in the ENS neurons. The reversal potential of GABA-induced depolarization was about -16 mV. Blockade of NKCC by bumetanide (50 μmol/L) or furosemide (300 μmol/L) suppressed the depolarizing responses to GABA. Bumetanide (50 μmol/L) shifted the reversal potential of GABA-induced depolarization in the hyperpolarizing direction. Neither the KCC blocker DIOA (20 μmol/L) nor the Cl/HCO exchanger inhibitor DIDS (200 μmol/L) suppressed GABA-evoked depolarization. The results suggest that ENS neurons continuously express NKCC2 since P1 and NKCC1 since P14, which contribute to the accumulation of Cl in ENS neurons and GABA-evoked depolarization in neonate and adult ENS neurons. These results provide the first direct evidence for the contribution of both NKCC2 and NKCC1 to the GABA-mediated depolarization.
Animals ; Bumetanide ; Neurons ; Rats ; Receptors, GABA-A ; Symporters ; gamma-Aminobutyric Acid

Using vacuous chewing movement(VCM) of rats as a possible animal model for tardive dyskinesia(TD), we tried to investigate the effects of haloperidol decanoate treatment on the rat brain: VCM(+) incidence, and morphological and neurochemical effect in the VCM(+) group. In our study, there were three treatment schedules of vehicle or haloperidol decanoate: 4, 7 or 9 total number of injections of vehicle or haloperidol decanoate were administered over 9, 18 or 24 weeks, respectively, with an injection given every 3 weeks. We rated VCM scores of rats at each injection time. Haloperidol groups were then further divided into VCM(-) rats and VCM(+) rats according to their VCM scores. Afterward, VCM(+) incidence was obtained in each haloperidol group. As time of neuroleptic treatment increased, the VCM scores and incidence of VCM(+) were found to be increased. All of the control, VCM(+) and VCM(-) rats were sacrificed to determine if treatments had morphological and neurochemical effects in the brain. Density of medium-sized neurons and levels of GABA in the striatum were reduced in the VCM(+) group 3 with total 9 injections given, compared to either VCM(-) group 3 or control group 3. These results suggest that hypofunction of GABAnergic neurons is associated with the development of VCM and possibly, TD.
Animals ; Appointments and Schedules ; Brain* ; gamma-Aminobutyric Acid ; Glutamic Acid ; Haloperidol* ; Incidence ; Mastication ; Models, Animal ; Neurons ; Rats*

Using vacuous chewing movement(VCM) of rats as a possible animal model for tardive dyskinesia(TD), we tried to investigate the effects of haloperidol decanoate treatment on the rat brain: VCM(+) incidence, and morphological and neurochemical effect in the VCM(+) group. In our study, there were three treatment schedules of vehicle or haloperidol decanoate: 4, 7 or 9 total number of injections of vehicle or haloperidol decanoate were administered over 9, 18 or 24 weeks, respectively, with an injection given every 3 weeks. We rated VCM scores of rats at each injection time. Haloperidol groups were then further divided into VCM(-) rats and VCM(+) rats according to their VCM scores. Afterward, VCM(+) incidence was obtained in each haloperidol group. As time of neuroleptic treatment increased, the VCM scores and incidence of VCM(+) were found to be increased. All of the control, VCM(+) and VCM(-) rats were sacrificed to determine if treatments had morphological and neurochemical effects in the brain. Density of medium-sized neurons and levels of GABA in the striatum were reduced in the VCM(+) group 3 with total 9 injections given, compared to either VCM(-) group 3 or control group 3. These results suggest that hypofunction of GABAnergic neurons is associated with the development of VCM and possibly, TD.
Animals ; Appointments and Schedules ; Brain* ; gamma-Aminobutyric Acid ; Glutamic Acid ; Haloperidol* ; Incidence ; Mastication ; Models, Animal ; Neurons ; Rats*