[Effects of gamma-thiomethyl-alpha-aminobutyric acid, gamma-thiomethyl-alpha-hydroxybutyric acid and pantothenic acid on streptomycin poisoning].
Explore the source record for details and available documents.
Amino Acids↗
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.
Clinical evaluation of gamma-vinyl-gamma-aminobutyric acid for control of epilepsy in dogs.
Gamma-vinyl-gamma-aminobutyric acid is a novel antiepileptic drug that exerts its effects by increasing the concentration of gamma-aminobutyric acid in the brain. The mechanism of action involves irreversible inhibition of the metabolic pathway of gamma-aminobutyric acid. The drug was administered to 14 dogs in conjunction with other anticonvulsants, in an attempt to control refractory epilepsy. Four of these dogs had clinically relevant evidence of decreased seizure frequency. In 4 dogs, response to the drug was no better than response to phenobarbital alone. In 2 dogs, seizure control improved, but gamma-vinyl-gamma-aminobutyric acid was withdrawn because of development of hemolytic anemia. For various reasons, the therapeutic effect in the remaining 4 dogs could not be evaluated. This study of only 14 dogs illustrates some of the problems that confound our ability to judge the efficacy of anticonvulsant treatment.
Aminocaproates↗
Somatic and dendritic actions of gamma-aminobutyric acid agonists and uptake blockers in the hippocampus in vivo.
In rats under urethane anaesthesia gamma-aminobutyric acid agonists and uptake blockers were microiontophoretically applied in the pyramidal layer of CA1 and in the apical dendrites using a twin set of multibarrelled micropipettes. Thus, the somatic and dendritic field potentials elicited by commissural stimulation were recorded simultaneously and the effects of iontophoretic applications at either site studied. Somatic applications of gamma-aminobutyric acid, isoguvacine or muscimol produced an inhibition of the somatic population spike; this showed rapid fade and was followed by an "off" response i.e. an enhancement of the population spike discharge and the occurrence of a second (and occasionally third) spike. The order of potency with regard to the "off" response was muscimol greater than isoguvacine much greater than gamma-aminobutyric acid. In contrast, the inhibition of the population spike produced by 4,5,6,7-tetrahydroisoxazolo(5,4-C) pyridin 3-OL showed little fade and no prominent "off" response. The fade and "off" response were not associated with significant changes in the dendritic field excitatory postsynaptic potential concommittantly recorded and were exclusively restricted to the immediate vicinity of the pyramidal layer. Ejection of gamma-aminobutyric acid and its agonists in the stratum radiatum produced a reduction of the field excitatory postsynaptic potential and the somatic spike, this effect however showed no fade (even during prolonged applications of high doses) and no "off" response. Somatic applications of the uptake blockers nipecotic acid or guvacine consistently produced: an increase in the effectiveness of the inhibition produced by gamma-aminobutyric acid and its analogues: a decrease in the latency to peak of the inhibition and an increase in the time to recovery; a full blockade of the fade and the "off" response. All of these effects were rapid and fully reversible without significant changes in either the field excitatory postsynaptic potential or the (control) somatic spikes. The more specific glial uptake blocker, 4,5,6,7-tetrahydroisoxazolo(4,5-C) pyridin 3-OL occasionally blocked the "off" response, however it was less potent and also tended to reduce the spike amplitude. Dendritic applications of the uptake blockers reduced the excitatory postsynaptic potential and the somatic spike but failed to produce prominent changes in the action of gamma-aminobutyric acid and its analogues.(ABSTRACT TRUNCATED AT 400 WORDS)
Acetylcholine↗
Hepatic encephalopathy: lack of changes of gamma-aminobutyric acid content in plasma and cerebrospinal fluid.
The aim of the study was to verify the role of gamma-aminobutyric acid in the pathogenesis of hepatic encephalopathy occurring in cirrhotic patients by attempting to correlate plasma and cerebrospinal fluid content of authentic gamma-aminobutyric acid with the neurological manifestations of hepatic encephalopathy. For this purpose, plasma and cerebrospinal fluid gamma-aminobutyric acid levels were measured by means of mass fragmentography in 17 cirrhotic patients with hepatic encephalopathy and in 6 cirrhotics without neurological symptoms. Moreover, in all patients, a second sample was obtained during the clinical course of hepatic encephalopathy. The mean plasma and cerebrospinal fluid gamma-aminobutyric acid levels were not different in patients with or without hepatic encephalopathy and did not change during the evolution of the neurological symptoms. The lack of changes in the gamma-aminobutyric acid content in plasma and cerebrospinal fluid during hepatic encephalopathy is in contrast with the hypothesized importance of increased entry into the brain of gamma-aminobutyric acid in the pathogenesis of hepatic encephalopathy.
Adult↗
The effect of arachidonic acid and free fatty acids on vesicular uptake of glutamate and gamma-aminobutyric acid.
The manner in which arachidonic acid and other free fatty acids influence the vesicular uptake of glutamate and gamma-aminobutyric acid (GABA) has been investigated. The cis-polyunsaturated fatty acid arachidonic acid (20:4), eicosapentanoic acid (20:5) and linolenic acid (18:3) at 150 nmol/mg protein (50 microM) inhibited the vesicular uptake of glutamate and GABA more than 70%. Reduced inhibition of vesicular uptake was seen with the cis-monounsaturated fatty acid oleic acid (18:1) and the trans-mono-unsaturated fatty acid elaidic acid (18:1). The saturated fatty acids stearic acid (16:0) and arachidic acid (20:0) had no significant effect on the uptake. The inhibition of vesicular uptake by arachidonic acid was prevented by the addition of fatty acid free bovine serum albumin. Arachidonic acid inhibited in a dose-dependent manner the generation of the transmembrane pH gradient of the synaptic vesicles. This inhibition was proportional to the inhibition of the vesicular uptake of glutamate and GABA. The saturated fatty acid arachidic acid showed no inhibition of delta pH generation. Arachidonic acid at 200 nmol/mg of protein did not increase the uptake-independent leakage of glutamate and GABA from the vesicles, showing that the effect of arachidonic acid is not caused by an unspecific detergent effect. These results suggest that arachidonic acid and other polyunsaturated fatty acids are acting like proton-ionophores on the vesicular uptake of these neurotransmitters. This finding may have implications for the increased fatty acid concentration during pathological conditions like ischemia and in long term potentiation.
Animals↗
Neuronal and glial systems for gamma-aminobutyric acid metabolism.
Explore the source record for details and available documents.
Alanine↗
Effect of protein and lactulose on the production of gamma-aminobutyric acid by faecal Escherichia coli.
The value of lactulose treatment in hepatic encephalopathy is widely recognised but its mode of action remains controversial. Much evidence supports a role for gamma-aminobutyric acid in hepatic encephalopathy, and lactulose could alter its bacterial production in the gut. Using the rat synaptic membrane assay and gas chromatography mass spectrometry, the production of gamma-aminobutyric acid by faecal Escherichia coli, with and without the addition of albumin, haemoglobin, whole blood, and lactulose under aerobic and anaerobic conditions was determined. Using an inorganic medium, maximal gamma-aminobutyric acid production occurred after a culture period of between 25 and 50 hours. The concentration after 30 hours of aerobic culture at 37 degrees C by a single strain was mean (SEM), 101 (5) mumol/l (99% confidence intervals 87-114 mumol/l; n = 8; interassay coefficient of variation 14.7%). gamma-aminobutyric acid production was significantly increased by the addition of albumin and haemoglobin. Under anerobic conditions, it was one fifth of that produced aerobically, but the addition of albumin and haemoglobin increased production by greater than 700%. Lactulose did not significantly attenuate gamma-aminobutyric acid production under aerobic or anaerobic conditions. gamma-aminobutyric acid determined by the rat synaptic membrane assay showed a highly significant correlation (r = 0.99) with that detected by gas chromatography mass spectrometry. These data confirm that gamma-aminobutyric acid is produced by faecal E coli and that protein enhances its production considerably, and suggest that lactulose does not exert its therapeutic effect by attenuating gamma-aminobutyric acid production.
Aerobiosis↗
Crystallization and preliminary X-ray analysis of gamma-aminobutyric acid transaminase.
gamma-Aminobutyric acid transaminase from pig liver, an alpha 2 dimeric enzyme of Mr 110,100, has been crystallized by the vapour diffusion method with polyethylene glycol as precipitant. The crystals are monoclinic, space group P2(1), unit cell dimensions a = 82.1 A, b = 230.0 A, c = 70.3 A, beta = 123.9 degrees and diffract to 2.5 A resolution. There are two dimers per asymmetric unit.
4-Aminobutyrate Transaminase↗
[Gamma-aminobutyric acid in the rat brain in hypokinesia].
Explore the source record for details and available documents.
Amino Acids↗
The effect of tetrahydroisoxazolopyridinol (THIP) in tardive dyskinesia: a new gamma-aminobutyric acid agonist.
gamma-Aminobutyric acid (GABA) agonists have been proposed for the treatment of tardive dyskinesia, but their therapeutic potential has been limited by side effects and toxicity. To elucidate further the role of GABA in neuroleptic-induced dyskinesias, we evaluated tetrahydroisoxazolopyridinol (THIP), a new, less toxic GABA analog and GABA receptor agonist, in both a dose-finding (single-dose) pilot study with five patients and a longer (four-week) placebo-controlled study with 13 patients. The patients were videotaped during a standardized examination; tardive dyskinesia, parkinsonian symptoms, and eye-blinking rates were rated blindly and randomly. The maximal short-term dose of THIP was 10 to 25 mg, whereas in the longer-term study the highest daily dose ranged from 20 to 120 mg. Tardive dyskinesia was unchanged during THIP treatment, but preexisting parkinsonism increased significantly and eye-blinking rates decreased. Psychiatric symptoms showed no significant changes, although tension and depression lessened. Side effects included sedation, confusion, dizziness, vomiting, and myoclonic jerks. Although THIP is not an effective new treatment for tardive dyskinesia, more specific GABA agonists should be evaluated in future studies of this syndrome.
Adult↗
Immunocytochemical localization of a Manduca sexta gamma-aminobutyric acid transporter.
Gamma-aminobutyric acid (GABA) is a major inhibitory neurotransmitter in insect central and peripheral nervous systems. Although much work has focused on the downstream targets of GABA, signal termination at insect GABAergic synapses has received very little attention. One of the major mechanisms of terminating synaptic transmission involves transport of the neurotransmitter molecules into presynaptic neurons or surrounding glia. Here we report the immunolocalization of a GABA transporter in the tobacco hornworm, Manduca sexta (MasGAT), using an affinity-purified antibody developed to the C-terminus. This is the first demonstration of an insect neurotransmitter transporter immunolocalization study. Results showed strong staining in the neuropil regions of embryonic, larval, and pharate adult central nervous system. Expression pattern in the pharate adult brain mostly mimicked that observed for GABA, with staining in parts of the optic and antennal lobes, mushroom body, lateral protocerebrum, and central complex. Certain longitudinal and lateral connectives of ganglia were observed to have immunostained fibers representing axons. These data support the view that GABA is involved in visual and olfactory processing in the insect brain.
Aging↗
The interaction of the general anesthetic etomidate with the gamma-aminobutyric acid type A receptor is influenced by a single amino acid.
The gamma-aminobutyric acid type A (GABAA) receptor is a transmitter-gated ion channel mediating the majority of fast inhibitory synaptic transmission within the brain. The receptor is a pentameric assembly of subunits drawn from multiple classes (alpha1-6, beta1-3, gamma1-3, delta1, and epsilon1). Positive allosteric modulation of GABAA receptor activity by general anesthetics represents one logical mechanism for central nervous system depression. The ability of the intravenous general anesthetic etomidate to modulate and activate GABAA receptors is uniquely dependent upon the beta subunit subtype present within the receptor. Receptors containing beta2- or beta3-, but not beta1 subunits, are highly sensitive to the agent. Here, chimeric beta1/beta2 subunits coexpressed in Xenopus laevis oocytes with human alpha6 and gamma2 subunits identified a region distal to the extracellular N-terminal domain as a determinant of the selectivity of etomidate. The mutation of an amino acid (Asn-289) present within the channel domain of the beta3 subunit to Ser (the homologous residue in beta1), strongly suppressed the GABA-modulatory and GABA-mimetic effects of etomidate. The replacement of the beta1 subunit Ser-290 by Asn produced the converse effect. When applied intracellularly to mouse L(tk-) cells stably expressing the alpha6beta3gamma2 subunit combination, etomidate was inert. Hence, the effects of a clinically utilized general anesthetic upon a physiologically relevant target protein are dramatically influenced by a single amino acid. Together with the lack of effect of intracellular etomidate, the data argue against a unitary, lipid-based theory of anesthesia.
Amino Acids↗
Functional modulation of human recombinant gamma-aminobutyric acid type A receptor by docosahexaenoic acid.
Human gamma-aminobutyric acid type A (GABAA) receptors were expressed in the baculovirus/Sf-9 insect cell expression system using recombinant cDNA of alpha1beta2gamma2s subunits. The effect of unsaturated fatty acids on GABAA receptor complexes was investigated electrophysiologically using conventional whole cell recording under voltage clamp. Three distinct effects of docosahexaenoic acid (DHA) on the GABA responses were observed. First, DHA, at a concentration of 10(-7) M or greater, accelerated the desensitization after the peak of the GABA-induced current. Second, DHA (10(-6) M) potentiated the peak amplitude of GABA response. This potentiation by DHA was inhibited in the presence of Zn2+ (10(-5) M); Cu2+ and Ni2+ mimicked the action of Zn2+. Zn2+ (10(-5) M) did not block the GABA response on alpha1beta2gamma2s receptor complexes. Third, DHA, at a concentration of 3 x 10(-6) M or higher, gradually suppressed the peak amplitude of GABA response. A protein kinase A inhibitor, a protein kinase C inhibitor, and a Ca2+ chelator did not modify the effects of DHA on GABA-induced chloride ion current. Six unsaturated fatty acids other than DHA were examined. Arachidonic acid mimicked the effect of DHA while e.g. oleic acid had no effect. The inhibition of the GABA response in the presence of DHA was also observed in cells expressing GABAA receptors of alpha1 and beta2 subunit combinations. The data show that the gamma subunit is essential for DHA and arachidonic acid to potentiate the GABA-induced Cl- channel activity and to affect the desensitization kinetics of the GABAA receptor.
Animals↗
Sequence and chromosomal assignment of a human novel cDNA: similarity to gamma-aminobutyric acid transporter.
Gamma-aminobutyric acid (GABA) is the predominant inhibitory neurotransmitter in the mammalian brain. Although initially thought to be confined to the central nervous system, GABAergic activity has also been described in other tissues throughout the body. In the present study, we report the cloning and localization of human GABA transporter cDNA and document its expression in various human tissues. A human liver cDNA library was initially screened by a 32P-labeled murine brain GABA transporter 3 (GAT-3) cDNA probe, and full-length cDNA was cloned by employing Marathon-Ready human kidney cDNA. The human GABA transporter cDNA encoded a 569 amino acid hydrophobic protein with 12 transmembrane domains (TMs). Search of published sequences revealed high homology with rat GAT-2, murine GAT-3 cDNA, human solute carrier family 6 member 13 (SLC6A13), and a human peripheral betaine/GABA transporter. Northern blot analyses demonstrated that the human GABA transporter is expressed strongly in the kidney and to a lesser extent in the liver and brain. The sequence was well matched with human chromosome 12p13.3, suggesting the human GABA transporter contains 14 exons. The above findings confirm the existence of and further characterize a specific GABA transporter in human tissues.
Amino Acid Sequence↗
Response of the cockroach brain gamma-aminobutyric acid system to isonicotinic acid hydrazide and mercaptopropionic acid.
The presence of gamma-aminobutyric acid (GABA) as well as glutamic acid decarboxylase (GAD) and GABA-transaminase (GABA-T) enzymes was demonstrated in the cockroach (Periplaneta americana) brain. Isonicotinic acid hydrazide (INH) in vivo (2.19 mumol/g) inhibited brain GAD activity, the inhibition lasted for about 2 hours and the normal activity levels reappeared at 4 h after INH administration. Brain GABA levels increased initially but then declined and were restored to normal levels at 4 h after INH administration. GABA-T activity was strongly inhibited by INH and a total 100% inhibition was observed at 2-3 h following INH treatment. The GABA-T activity, however, began to recover after 3 h but only 37% of the total enzyme activity was released from inhibition. Mercaptopropionic acid (MPA) in vivo (32 micrograms/g) inhibited brain GAD activity and depleted GABA level also. Results indicate that INH response of the cockroach brain GABA system is similar to that reported for the chick brain but differs from that of the mammalian brain.
3-Mercaptopropionic Acid↗
Further characterization of [3H]gamma-aminobutyric acid release from isolated neuronal growth cones: role of intracellular Ca2+ stores.
We have recently shown that growth cones isolated from neonatal rat forebrain possess uptake and release mechanisms for the neurotransmitter gamma-aminobutyric acid. About half of the K+-induced release of [3H]gamma-aminobutyric acid from isolated growth cones is dependent on extracellular Ca2+. The remaining component of the [3H]gamma-aminobutyric acid release is unaffected by removal of extracellular Ca2+ and is resistant to blockade by the voltage-sensitive Ca2+-channel blocker methoxyverapamil. In the present series of experiments we have used caffeine to assess the possible role of intracellular stores of Ca2+ in supporting that component of the K+-induced release of [3H]gamma-aminobutyric acid from isolated growth cones that is independent of extracellular Ca2+. We have chosen caffeine because of its well established effect of releasing Ca2+ from smooth endoplasmic reticulum in muscle. We found that caffeine can release [3H]gamma-aminobutyric acid from isolated growth cones. This effect persists in Ca2+-free medium, in the presence of methoxyverapamil and in the absence of Na+. Furthermore, isobutylmethylxanthine could not substitute for caffeine suggesting that the caffeine effect is not due to phosphodiesterase inhibition and the subsequent rise in intracellular cyclic nucleotides. A combination of the mitochondrial poisons, Antimycin A and sodium azide had no effect on the release of [3H]gamma-aminobutyric acid induced either by caffeine or by high K+. We conclude that caffeine causes the release of Ca2+ from a non-mitochondrial store within the growth cone and that this Ca2+ store supports that component of the K+-induced release of [3H]gamma-aminobutyric acid that is independent of extracellular Ca2+.
Animals↗
Identification of benzodiazepine binding site residues in the gamma2 subunit of the gamma-aminobutyric acid(A) receptor.
gamma-Aminobutyric acid(A) receptor gamma-subunits are important for benzodiazepine (BZD) binding and modulation of the gamma-aminobutyric acid-mediated Cl(-) current. Previously, by using gamma2/alpha1 chimeric subunits, we identified two domains of the gamma2-subunit, Lys-41-Trp-82 and Arg-114-Asp-161, that are, in conjunction, necessary and sufficient for high-affinity BZD binding. In this study, we generated additional gamma2/alpha1 chimeric subunits and gamma2 point mutants to identify specific residues within the gamma2 Lys-41-Trp-82 region that contribute to BZD binding. Mutant gamma2 and gamma2/alpha1 chimeric subunits were expressed with wild-type alpha1 and beta2 subunits in HEK 293 cells, and the binding of several BZDs was measured. We present evidence that the gamma2 region Met-57-Ile-62 is important for flunitrazepam binding and that, in particular, gamma2 Met-57 and gamma2 Tyr-58 are essential determinants for conferring high-affinity binding. Furthermore, we identify an additional residue, gamma2 Ala-79, that not only is important for high-affinity binding by flunitrazepam (a strong positive modulator) but also plays a crucial role in the binding of the imidazobenzodiazepines Ro15-1788 (a zero modulator) and Ro15-4513 (a weak negative modulator) in the BZD binding pocket. Results from site-directed mutagenesis of gamma2 Ala-79 suggest that this residue may be part of a microdomain within the BZD binding site that is important for binding imidazobenzodiazepines. This separation of drug-specific microdomains for competitive BZD ligands lends insight into the structural determinants governing the divergent effects of these compounds.
Amino Acid Sequence↗
[Relation between gamma-aminobutyric acid and tyrosine metabolism and changes in the brain and liver amino acid content in intact and adrenalectomized rats].
Explore the source record for details and available documents.
Adrenal Glands↗