Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “AMINOBUTYRIC ACID”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 253 records · Page 14Linked to original sources
PubMed2002

Convulsant and subconvulsant doses of norfloxacin in the presence and absence of biphenylacetic acid alter extracellular hippocampal glutamate but not gamma-aminobutyric acid levels in conscious rats.

Fluoroquinolones are antibiotics with central excitatory side effects. These adverse effects presumably result from inhibition of gamma-aminobutyric acid (GABA) binding to GABA(A) receptors. This GABA antagonistic effect is greatly potentiated by the active metabolite of fenbufen, biphenylacetic acid (BPAA). Nevertheless, it remains questionable whether GABA receptor antagonism alone can explain the convulsant activity potentials of these antimicrobial agents. The present study was undertaken to investigate the possible effects of norfloxacin, both in the absence and in the presence of BPAA, on the extracellular hippocampal levels of GABA and glutamate, the main central inhibitory and excitatory amino acid neurotransmitters, respectively. This in vivo microdialysis approach with conscious rats allows monitoring of behavioral alterations and concomitant transmitter modulation in the hippocampus. Peroral administration of 100 mg of BPAA per kg of body weight had no effect on behavior and did not significantly alter extracellular GABA or glutamate concentrations. Intravenous perfusion of 300 mg of norfloxacin per kg did not change the rat's behavior or the concomitant neurotransmitter levels in about half of the experiments, while the remaining animals exhibited severe seizures. These norfloxacin-induced convulsions did not affect extracellular hippocampal GABA levels but were accompanied by enhanced glutamate concentrations. Half of the rats receiving both 100 mg of BPAA per kg and 50 mg of norfloxacin per kg displayed lethal seizures, while the remaining animals showed no seizure-related behavior. In the latter subgroup, again no significant alterations in extracellular GABA levels were observed, but glutamate overflow remained significantly elevated for at least 3 h. In conclusion, norfloxacin exerts convulsant activity in rats, accompanied by elevations of extracellular hippocampal glutamate levels but not GABA levels, even in the presence of BPAA.

Administration, Oral↗
PubMed1981

delta-Aminolaevulinic acid uptake, toxicity, and effect on [14C]gamma-aminobutyric acid uptake into neurons and glia in culture.

delta-Aminolaevulinic acid (ALA) uptake into neurons and glia in primary culture as well as ALA toxicity and its effects on gamma-aminobutyric acid (GABA) uptake were examined. [4-14C]ALA uptake into neurons and glia was nonsaturable, partially Na+- and temperature-dependent, and appeared to comprise mainly diffusion into the cell. 2,4-Dinitrophenol caused some inhibition of [4-14C]ALA uptake whereas ouabain, KCN, or amino acids at 1 mM concentration were without effect. ALA (1 mM) caused a slight inhibition of [U-14C]GABA uptake into neurons (14%) and glia (9%), but was without effect at lower concentrations. It is unlikely that, in acute porphyria, ALA reaches sufficiently high levels in nervous tissue to interfere with the reuptake of GABA into neurons or glia. ALA was shown to be toxic, judged by the loss of cells, to both neurons and glia at concentrations as low as 10 microM. Such a concentration of ALA may be expected to occur in the CSF of porphyric patients in the acute attack. However, results obtained with dispersed cells in culture may not necessarily reflect the situation in vivo where the cell may have a far greater resistance to the effects of toxic agents.

Aminolevulinic Acid↗
PubMed1982

Experimental hepatic encephalopathy: changes in the binding of gamma-aminobutyric acid.

Two populations of receptors for gamma-aminobutyric acid, one with low- and the other with high-affinity characteristics, are detectable in frozen, thawed, Triton-treated synaptic membrane preparations from normal brain. It is now reported that membrane preparations from rats with mild galactosamine-induced hepatic encephalopathy show an increase in the number of low- and high-affinity gamma-aminobutyric acid binding sites, whereas those from rats with severe encephalopathy show only high-affinity binding sites. Thus, hepatic encephalopathy appears to involve partial degeneration of the gamma-aminobutyric acid-containing presynaptic nerve terminals.

Bicuculline↗
PubMed1977

4-amino-hex-5-enoic acid, a selective catalytic inhibitor of 4-aminobutyric-acid aminotransferase in mammalian brain.

Incubation of rat brain 4-aminobutyrate aminotransferase with 4-amino-hex-5-enoic acid, a substrate analog of 4-aminobutyric acid, results in a time-dependent irreversible loss of enzymatic activity. In the presence of 0.1 mM inhibitor the half-life of the inactivation process is approximately 6 min. Low concentrations of L-glutamic acid or 4-aminobutyric acid protect against this inactivation, while 2-oxoglutarate prevents this protection, suggesting that only the pyridoxal form of the enzyme is susceptible to inhibition by 4-amino-hex-5-enoic acid. The irreversible inhibition of mammalian 4-aminobutyrate aminotransferase by 4-amino-hex-5-enoic acid is selective. There is no inhibition of this enzyme from Pseudomonas fluorescens with the inhibitor at mM concentrations. Even at 10 mM there is no irreversible inhibition of mammalian glutamate decarboxylase or of aspartate aminotransferase, while alanine aminotransferase is inhibited over 500 times more slowly than rat brain 4-aminobutyrate transaminase.

4-Aminobutyrate Transaminase↗
PubMed1997

Time course of alpha-fluorinated valproic acid in mouse brain and serum and its effect on synaptosomal gamma-aminobutyric acid levels in comparison to valproic acid.

To prevent the hepatotoxicity of valproic acid (VPA), a fluorine substituent was introduced at the alpha-position to eliminate the formation of putative toxic metabolites through mitochondrial beta-oxidation. Although the alpha-fluorinated VPA analogue (alpha-fluoro VPA) is more acidic (pK(a) = 3.55) than VPA (pK(a) = 4.80), the lipophilicity of these two compounds, as determined by their log P values, were similar when compared at pH 2.5. Brain, serum and urine samples were prepared from mature male CD-1 mice treated with either alpha-fluoro VPA or VPA for quantitation of drug concentrations. Brain synaptosomes were isolated to determine gamma-aminobutyric acid levels. After equivalent doses of 0.83 mmol/kg, alpha-fluoro VPA was characterized by its slower access into mouse brain, compared to VPA. The peak concentration of alpha-fluoro VPA in mouse brain was achieved 45 min later than in the serum, whereas the peak brain level of VPA coincided with the peak serum level occurring within 15 min. Simultaneous curve fitting of both brain and serum drug concentrations using a two-compartment model indicated that alpha-fluoro VPA, like VPA, may be asymmetrically transported across the blood-brain-barrier. This property of alpha-fluoro VPA was also reflected in its low brain-to-serum concentration ratio of 0.09 at the peak brain drug concentration (0.16 for VPA). The primary beta-oxidation metabolite of VPA was not found in the serum and urine of mice treated with alpha-fluoro VPA. Although the glucuronide was a major metabolite of VPA (28.5% of the dose), alpha-fluoro VPA was observed to conjugate extensively with L-glutamine (33.3% of the dose). Alpha-fluoro VPA appeared to persist in the general circulation, which, in turn, may contribute to the apparent slow elimination of the drug from the brain. The fluorinated compound was demonstrated to have anticonvulsant activity in the 1,5-pentamethylenetetrazole seizure test and to be capable of increasing brain synaptic gamma-aminobutyric acid, the ED50 being 1.70 mmol/kg. These results suggest that alpha-fluoro VPA has potential as a new anticonvulsant drug.

Animals↗
PubMed1983

In vitro and in vivo effects on brain GABA metabolism of (S)-4-amino-5-fluoropentanoic acid, a mechanism-based inactivator of gamma-aminobutyric acid transaminase.

The effects of intraperitoneal administration of (S)-4-amino-5-fluoropentanoic acid, a mechanism-based covalent inactivator of gamma-aminobutyric acid transaminase (GABA-T), on whole brain GABA metabolism in mice were investigated. A dose-dependent and time-dependent irreversible inactivation of GABA-T was observed with a concomitant increase in whole brain GABA levels. The compound exhibited no in vitro nor in vivo time-dependent inhibition of glutamate decarboxylase (GAD), alanine transaminase, or aspartate transaminase (Asp-T). It was, however, a potent competitive reversible inhibitor of GAD and a weak competitive inhibitor of Asp-T. The chloro analogue, (S)-4-amino-5-chloropentanoic acid, was ineffective.

4-Aminobutyrate Transaminase↗
PubMed2006

A novel function of ionotropic gamma-aminobutyric acid receptors involving alveolar fluid homeostasis.

Polarized distribution of chloride channels on the plasma membrane of epithelial cells is required for fluid transport across the epithelium of fluid-transporting organs. Ionotropic gamma-aminobutyric acid receptors are primary ligand-gated chloride channels that mediate inhibitory neurotransmission. Traditionally, these receptors are not considered to be contributors to fluid transport. Here, we report a novel function of gamma-aminobutyric acid receptors involving alveolar fluid homeostasis in adult lungs. We demonstrated the expression of functional ionotropic gamma-aminobutyric acid receptors on the apical plasma membrane of alveolar epithelial type II cells. gamma-Aminobutyric acid significantly increased chloride efflux in the isolated type II cells and inhibited apical to basolateral chloride transport on type II cell monolayers. Reduction of the gamma-aminobutyric acid receptor pi subunit using RNA interference abolished the gamma-aminobutyric acid-mediated chloride transport. In intact rat lungs, gamma-aminobutyric acid inhibited both basal and beta agonist-stimulated alveolar fluid clearance. Thus, we provide molecular and pharmacological evidence that ionotropic gamma-aminobutyric acid receptors contribute to fluid transport in the lung via luminal secretion of chloride. This finding may have the potential to develop clinical approaches for pulmonary diseases involving abnormal fluid dynamics.

Adenoviridae↗
PubMed1985

Pharmacological and ionic features of gamma-aminobutyric acid receptors influencing electrical properties of melanotrophs isolated from the rat pars intermedia.

Characteristics of the gamma-aminobutyric acid receptors on melanotrophs of the rat pars intermedia were studied by intracellular recording. Muscimol and 3-amino-1-propanesulfonic acid, but not baclofen or glycine, mimicked the depolarization and conductance increase produced by gamma-aminobutyric acid on the melanotrophs. These effects appeared to be due to an increase in chloride ion conductance since the null potentials for all three drugs were the same and were affected by changes in external or internal chloride ion concentration but not by changes in the concentrations of other ions present in the recording solution or by the addition of the calcium-channel blocker cobalt. Bicuculline abolished the effect of muscimol. Picrotoxin reduced the effect of gamma-aminobutyric acid; so too did furosemide. Muscimol mimicked the ability of gamma-aminobutyric acid to reduce the depolarization produced by excess potassium and this effect was also blocked by bicuculline. Rat melanotrophs thus appear to possess gamma-aminobutyric acid receptor-ionophore complexes similar to the classical sort found in neurons in the mammalian central nervous system. Furthermore, the parallels between the electrical responses observed and secretory effects previously noted, reinforce the view that electrical activity may participate in stimulus-secretion coupling in melanotrophs.

Animals↗
PubMed1986

Neurons accumulating [3H]gamma-aminobutyric acid (GABA) in supragranular layers of cat primary auditory cortex (AI)

The classes of neurons accumulating exogenously injected, tritiated gamma-aminobutyric acid [( 3H]GABA) were studied in the supragranular layers in the primary auditory field of the adult cat. The size, laminar locus, and somatodendritic profiles of labeled neurons were studied light microscopically in frozen- or Vibratome-sectioned, 30 micron thick material, and in semithin, 1-2 micron thick, plastic-embedded high-resolution autoradiographic preparations. The chief goals of the study were to determine which types of cells could be identified as accumulating [3H]GABA in layers I, II and III, and to establish possible relationships between these cells and neurons described in Golgi studies of these layers, and the neurons found, in parallel investigations of the connections of the primary auditory field, to participate as ipsilateral corticocortical and commissural cells of origin. The principal findings are: that neurons in every layer in the primary auditory field take up tritiated gamma-aminobutyric acid; that their Nissl-counterstained somata have a smaller average area, and a smaller range of areas, than do the unlabeled cells; that more than one type of labeled neuron-as defined by somatic size and shape, height:width ratios, and nuclear membrane morphology-could be identified in each layer; that none of the labeled neurons had a soma with a pyramidal configuration; that the labeled cells are comparable in size, shape, and laminar distribution to some populations of non-pyramidal ipsilateral corticocortical cells of origin in layers II and III, and perhaps to certain classes of commissurally projecting, layer III non-pyramidal neurons; and finally, that only a rather small proportion-perhaps 10% or less, except in layer I-of the supragranular cells appear to accumulate labeled material. With regard to the identity of particular classes of neurons accumulating silver grains above background in the individual layers, in layer I, 2 of the 4 types of neurons characterized in Golgi preparations take up gamma-aminobutyric acid and the remaining 2 types may also, and the relative number of labeled cells appears to be higher than in the other layers; in layer II, 2 of the 9 varieties are labeled, and 4 other types may also be; and in layer III, 2 of the 11 types take up gamma-aminobutyric acid, and 5 other varieties may as well. Three types of non-pyramidal layer II cells that project ipsilaterally from AI to the second auditory cortical field, AII, possibly accumulate gamma-aminobutyric acid; 3 types of commissural non-pyramidal cells of origin linking AI to AI appear to be labeled by gamma-aminobutyric acid.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

[beta]-Aminobutyric Acid Induces the Accumulation of Pathogenesis-Related Proteins in Tomato (Lycopersicon esculentum L.) Plants and Resistance to Late Blight Infection Caused by Phytophthora infestans.

Tomato (Lycopersicon esculentum L.) plants were sprayed with aqueous solutions of isomers of aminobutyric acid and were either analyzed for the accumulation of pathogenesis-related (PR) proteins or challenged with the late blight fungal agent Phytophthora infestans. The [beta] isomer of aminobutyric acid induced the accumulation of high levels of three proteins: P14a, [beta]-1,3 glucanase, and chitinase. These proteins either did not accumulate or accumulated to a much lower level in [alpha]- or [gamma]-aminobutyric acid-treated plants. Plants pretreated with [alpha]-, [beta]-, and [gamma]-aminobutyric acid were protected up to 11 d to an extent of 35, 92, and 6%, respectively, against a challenge infection with P. infestans. Protection by [beta]-aminobutyric acid was afforded against the blight even when the chemical was applied 1 d postinoculation. Examination of ethylene evolution showed that [alpha]-aminobutyric acid induced the production of 3-fold higher levels of ethylene compared with [beta]-aminobutyric acid, whereas [gamma]-aminobutyric acid induced no ethylene production. In addition, silver thiosulfate, a potent inhibitor of ethylene action, did not abolish the resistance induced by [beta]-aminobutyric acid. The results are consistent with the possibility that [beta]-aminobutyric acid protects tomato foliage against the late blight disease by a mechanism that is not mediated by ethylene and that PR proteins can be involved in induced resistance.

Journal Article↗
PubMed1989

Effect of a brief hypoxic/hypotensive episode on the in vivo release of cerebral cortical gamma-aminobutyric acid and glycine.

gamma-Aminobutyric acid (GABA) and glycine levels in rat cerebral cortical superfusates rose during a 10-min period to reach stable concentrations of approximately 0.55 microM and approximately 12.3 microM, respectively. In cerebrospinal fluid withdrawn from the fourth ventricle, the GABA concentration was 0.1 microM, and that of glycine, 10.55 microM. GABA, and to a lesser extent glycine, concentrations increased in the cortical superfusates during and immediately following exposure of the rats to a 5-min period of 5% oxygen in nitrogen inhalation.

Animals↗
PubMed1987

Multiple mechanisms of antagonism of gamma-aminobutyric acid (GABA) responses.

Gamma-aminobutyric acid (GABA) is one of the most important neurotransmitters in the brain. In an effort to understand the operation of the GABA receptor-ionophore complex, the antagonism of GABA responses by four substances was studied in bullfrog dorsal root ganglion cells by concentration-clamp and internal-perfusion techniques. Two antagonists (bicuculline and Zn2+) were competitive; two (picrotoxin and penicillin) were noncompetitive. However, significant changes in the kinetics of activation and inactivation were produced by the antagonists, including those that were competitive. The causes of these changes may be important clues to the structure and operation of the GABA receptor-ionophore complex.

Animals↗
PubMed1982

Hepatic encephalopathy and the gamma-aminobutyric-acid neurotransmitter system.

gamma-Aminobutyric acid (GABA), the principal inhibitory neurotransmitter of the mammalian brain, is synthesised by gut bacteria. In a rabbit model the development of hepatic encephalopathy was associated with increased levels of GABA in plasma, increased permeability of the blood-brain barrier, increased numbers of binding-sites for GABA and benzodiazepines in the brain, and a pattern of neural activity similar to that induced by drugs which activate the GABA neurotransmitter system. It is postulated that in liver failure gut-derived GABA passes through a permeable blood-brain barrier and induces its own receptors in the brain, that gut-derived GABA contributes to the neural inhibition of hepatic encephalopathy, and that an increased number of drug-binding sites mediates enhanced sensitivity to barbiturates and benzodiazepines in liver failure.

4-Aminobutyrate Transaminase↗
PubMed1997

[Determination of gamma-aminobutyric acid and glutamic acid in human cerebrospinal fluid by high performance liquid chromatography].

Gamma-aminobutyric acid (Gaba) and glutamic acid (Glu) are believed to be the major neurotransmitter. Levels in cerebrospinal fluid (CSF) may reflect their metabolism in various neurotic and psychiatric diseases. Measurements of Gaba and Glu in body fluids will help to elucidate their metabolic role and diagnostic value. In the present work, the concentrations of glutamic acid and gamma-aminobutyric acid in human cerebrospinal fluid were determined by reversed-phase high performance liquid chromatography using pre-column derivatized with dansyl chloride and UV detection at 254 nm. The mobile phase was A:CH3OH and B: THF/CH3OH/0.05 mol/L NaAc (pH 6.2) (5/75/420, V/V) with gradient elution. The flow rate was 1 mL/min. CSF samples were deproteinizated with methanol. After centrifugation at 15000 r/min for 10 min, the supernatant was introduced into a screw-capped vial and evaporated to near dryness at 80 degrees C. Derivatization was carried out by the addition of 250 microL of bicarbonate solution (pH 9.8) and 250 microL of dansyl chloride solution (4 g/L) followed by heating at 40 degrees C water bath for 30 min. Extraction was performed with 300 microL of ethyl acetate and the organic layer separated was dried at room temperature under nitrogen. The dry residue was dissolved and injected into the HPLC system. The linear range of the method was 5-1000 micromol/L (r = 0.9988) for Glu and 1-600 micromol/L (r = 0.9984) for Gaba. The lower limit of detection were 0.002 micromol/L and 0.001 micromol/L respectively. The recoveries were 96.9%-98.8% and 97.5%-98.8% and the coefficients of variation of peak height measurements were 2.2%-3.4% and 3.8%-5.6% respectivery. The method enables a simple, rapid and reproducible quantification of Glu and Gaba neurotransmitter.

Chromatography, High Pressure Liquid↗
PubMed1979

Independent inhibition of prolactin secretion by dopamine and gamma-aminobutyric acid in vitro.

gamma-Aminobutyric acid (GABA) inhibits PRL release from incubated hemipituitaries in a dose-dependent manner. The maximum inhibition obtained with GABA is less than that obtained with dopamine. Its affinity is 100 times lower. The effect is blocked by picrotoxin but not by a dopamine inhibitor; alpha-flupentixol but not picrotoxin antagonizes dopamine inhibition. This indicates that dopamine and GABA inhibit PRL release through independent receptors. The hypothalamic extract contains sufficient GABA to inhibit PRL release in our in vitro conditions. Picrotoxin, however, does not significantly inhibit the nondopaminergic PRL-inhibiting activity of mediobasal hypothalamic extracts. Another nondopaminergic PRL-inhibiting factor, therefore, seems to be present in the hypothalamus.

Animals↗
PubMed1995

Subunit composition determines picrotoxin and bicuculline sensitivity of Drosophila gamma-aminobutyric acid receptors.

Few gamma-aminobutyric acid (GABA) receptor subunits have been cloned from insects. These include Resistance to dieldrin, or Rdl, and a homologue of the vertebrate GABAA receptor beta subunit. Unlike most vertebrate GABAA receptor subunits, Rdl forms a highly functional homomultimeric receptor. This receptor is picrotoxin (PTX) sensitive but bicuculline (BIC) insensitive and cannot be readily classified within the known GABAA receptor subtypes. In contrast, functional expression of the beta subunit homologue has not been reported. We report that coinfection of cells with recombinant baculoviruses containing Rdl plus beta subunits induces GABA receptors with distinct pharmacological and kinetic properties. Coinfection produces two separate receptor populations: one highly sensitive to PTX but BIC insensitive (Rdl homomultimers) and the other PTX insensitive and BIC sensitive (Rdl plus beta heteromultimers). Putative Rdl plus beta channels also show reduced GABA sensitivity, slow desensitization, rapid bursting, and shorter mean open time. These studies not only localize PTX and BIC sensitivity to two distinct GABA receptor subunits but also demonstrate assembly of two highly divergent GABA receptor subunits. Furthermore, the difference in channel conductance and gating between in vivo and recombinant channels implies the existence of uncharacterized GABA receptor subunits in Drosophila.

Animals↗
PubMed1980

Do motor-nerve terminals have gamma-aminobutyric acid receptors?

1 gamma-Aminobutyric acid (GABA, 0.1 to 1 mM) had no significant effect on the amplitude, rise time, half decay time or frequency of miniature endplate potentials (m.e.p.ps) at the frog or mouse neuromuscular junctions in vitro. 2 Addition of GABA (1 mM) to preparations previously treated with 11 mM K+-Ringer did not cause any further increase in m.e.pp. frequency. GABA also failed to increase the m.e.p.p. frequency in a low Cl--Ringer. 3 GABA (0.1 to 1 mM) did not reduce the high m.e.p.p. frequency induced by veratrine (20 to 40 mg/l). 4 GABA (0.5 to 1 mM) did not affect the amplitude of the extracellularly-recorded nerve terminal spike, whereas 15 mM [K+] reduced the spike. 5 The quantal content (m) of the evoked endplate potential was not significantly altered by GABA; 9 mM [K+] significantly increased m. 6 When external d.c. potential differences were recorded in a three-chambered bath, GABA (0.1 to 1 mM) produced a very small depolarization if applied to the phrenic nerve trunk, but not if applied to the pre-terminal axon/motor nerve terminal region. Carbachol (0.3 to 1 mM) evoked a small depolarization when applied to the nerve terminal chamber. 7 These results fail to provide evidence for the existence of GABA receptors on motor nerve terminals.

Animals↗