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At least 289 records · Page 16Linked to original sources
PubMed1984

gamma-Aminobutyric acid receptor binding antagonism by the amidine steroid RU5135.

The novel convulsant amidine steroid RU5135 inhibited gamma-aminobutyric acid receptor binding in membranes from seven regions of rat brain (IC50 = 11 +/- 2 nM against [3H]muscimol and 0.8 +/- 0.2 nM against [3H]bicuculline methochloride), apparently lowering the number of binding sites labeled with gamma-aminobutyric acid receptor agonists or antagonists. The steroid reversed the enhancement of benzodiazepine receptor binding by gamma-aminobutyric acid, pentobarbital, and etazolate, but did not inhibit the binding of the convulsant [35S]t-butyl bicylophosphorothionate. Thus, RU5135 shows very potent in vitro actions more resembling those of the gamma-aminobutyric acid site antagonist, bicuculline, than the chloride channel antagonist, picrotoxin.

Androstanes↗
PubMed1971

-aminobutyric acid as a required germinant for mutant spores of Bacillus megaterium.

Germinated spores of Bacillus megaterium QM B1551 were irradiated with ultraviolet light, and spore-forming survivors were screened for germination requirements. Spore strains which failed to germinate in a variety of defined solutions germinative for spores of the parent strain were obtained. Mutant spores germinated readily in solutions containing yeast extract or one of numerous complex preparations. gamma-Aminobutyric acid, obtained from yeast extract by column chromatography, was shown to be required for germination by the mutant spores. gamma-Aminobutyric acid and l-alanine at final concentrations of 1 mm each, in solutions of KI (40 mm), equaled the potency of yeast extract (1 mg/ml) in the germination of the mutant spores. One of several other amino acids could be substituted, though less effectively, for l-alanine. alpha-Aminobutyric acid, beta-aminobutyric acid, beta-alanine, and 5-aminovaleric acid were ineffective substitutes for gamma-aminobutyric acid in mutant spore germination.

Alanine↗
PubMed1998

Enkephalin analogs containing 4,4-difluoro-2-aminobutyric acid: synthesis and fluorine effect on the biological activity.

Analogs of Met-enkephalin and [D-Pen2, D-Pen5]enkephalin (DPDPE) containing the partially fluorinated amino acid 4,4-difluoro-2-aminobutyric acid (DFAB) in the 2- or 3-position of the peptide sequence were synthesized and their opioid activities and receptor selectivities were determined in vitro. The linear fluorinated [D-DFAB2, Met5-NH2]enkephalin showed mu and delta agonist potencies comparable to those of natural [Leu5]enkephalin. The partially fluorinated DPDPE analogs behaved differently as compared with their non-fluorinated correlates. While L-amino acid substitution in position 3 of DPDPE usually resulted in higher delta agonist potency than D-amino acid substitution. [D-DFAB3]DPDPE turned out to be a more potent delta agonist than [L-DFAB3]DPDPE. Furthermore, [D-DFAB3]DPDPE showed over 100-fold higher delta agonist potency than [D-Abu3]DPDPE (Abu = 2-aminobutyric acid), indicating that the fluorine substituents interact favorably with a delta opioid receptor subsite.

Aminobutyrates↗
PubMed1985

Central action of gamma-aminobutyric acid ligands to alter basal water and electrolyte absorption in the rat ileum.

The gamma-aminobutyric acid agonist muscimol and the gamma-aminobutyric acid antagonist bicuculline were studied to determine their effects on basal net water and electrolyte transport in the rat ileum. Whereas the intraperitoneal injection of muscimol caused a reversible, dose-dependent decrease in net water absorption, bicuculline produced a reversible, dose-dependent increase in net water and ion absorption. The threshold doses of muscimol and bicuculline were greater than 2.1 and 2.2 micrograms/kg, respectively. Lower doses of muscimol (0.1 microgram) or bicuculline (0.3 microgram) administered into the cerebrospinal fluid had the same effect as higher doses given systemically. Vagotomy prevented the effect of intracerebroventricular muscimol. Atropine (6 micrograms intracerebroventricularly) alone did not alter basal water absorption but abolished the muscimol effect, suggesting that muscimol promoted the release of acetylcholine from central cholinergic neurons. Atropine did not prevent the bicuculline effect. We conclude that (a) muscimol decreases ileal water absorption and bicuculline enhances ileal water absorption by an action at a gamma-aminobutyric acid receptor in the central nervous system, (b) the muscimol effect is due to an alteration in parasympathetic vagal outflow to the intestine, (c) the muscimol effect is mediated by a central cholinergic interneuron, and (d) the bicuculline effect is not mediated by the release of acetylcholine from central cholinergic neurons.

Animals↗
PubMed1983

Succinic semialdehyde dehydrogenase deficiency: an inborn error of gamma-aminobutyric acid metabolism.

Gamma-hydroxybutyric aciduria is a disorder of gamma-aminobutyric acid metabolism in which a compound of known neuropharmacologic activity accumulates. We have studied two patients in whom high levels of gamma-hydroxybutyric acid were found in blood, urine and cerebrospinal fluid. A coupled assay has been developed which estimates succinic semialdehyde dehydrogenase activity in isolated human lymphocytes. The mean activity of succinic semialdehyde dehydrogenase in a control and the four parents and two healthy siblings of these patients was 8.8 +/- 1.9 pmol . min-1 . mg-1 protein. In the patients the activities were 0.8 and 1.1 pmol . min-1 . mg-1 protein, approximately 9-13% of control. In the presence of saturating amounts of NAD+, lymphocyte sonicates, derived from the patients accumulated a significant amount of 14C-succinic semialdehyde from 14C-gamma aminobutyric acid, whereas none could be detected in controls. The data suggest a deficiency of succinic semialdehyde dehydrogenase in these patients, the first documented defect of the metabolism of gamma-aminobutyric acid in man.

4-Aminobutyrate Transaminase↗
PubMed2005

Gamma aminobutyric acid regulates glucosensitive neuropeptide Y neurons in arcuate nucleus via A/B receptors.

Gamma aminobutyric acid (GABA) is localized in neuropeptide Y (NPY) neurons of the hypothalamic arcuate nucleus (ARC). We examined regulation of ARC NPY neurons by GABA. Light and electron microscopic immunohistochemistry confirmed that GABA-containing nerve terminals contacted NPY-containing neurons in the ARC. Lowering glucose (1 mM) increased cytosolic Ca2+ concentration ([Ca2+]i) in isolated ARC neurons that were immunoreactive to NPY. The [Ca2+]i increases were inhibited by GABA, the gamma-aminobutyric acid type A receptor (GABAA) agonist muscimol and the gamma-aminobutyric acid type B receptor (GABAB) agonist baclofen. Neither the GABAA antagonist bicuculline nor the GABAB antagonist CGP35348 counteracted the GABA inhibition when applied alone, but did so when applied together. These results indicate that GABA regulates ARC glucose-sensitive NPY neurons via GABAA and GABAB receptors, which could function to attenuate the orexigenic NPY pathway when it is not beneficial.

Animals↗
PubMed1990

(R)-N-[4,4-bis(3-methyl-2-thienyl)but-3-en-1-yl]nipecotic acid binds with high affinity to the brain gamma-aminobutyric acid uptake carrier.

(R)-N-[4,4-Bis(3-methyl-2-thienyl)but-3-en-1-yl]nipecotic acid (NO 328) has previously been shown to be a potent anticonvulsant in both mice and rats. Here, we report that NO 328 is a potent inhibitor of gamma-[3H]aminobutyric acid [( 3H]GABA) uptake in a rat forebrain synaptosomal preparation (IC50 = 67 nM) and in primary cultures of neurons and astrocytes. Inhibition of [3H]GABA uptake by NO 328 is apparently of a mixed type when NO 328 is preincubated before [3H]GABA uptake; the inhibition is apparently competitive without preincubation. NO 328 itself is not a substrate for the GABA uptake carrier, but NO 328 is a selective inhibitor of [3H]GABA uptake. Binding to benzodiazepine receptors, histamine H1 receptors, and 5-hydroxytryptamine1A receptors was inhibited by NO 328 at 5-30 microM, whereas several other receptors and uptake sites were unaffected. [3H]NO 328 showed saturable and reversible binding to rat brain membranes in the presence of NaCl. The specific binding of [3H]NO 328 was inhibited by known inhibitors of [3H]GABA uptake; GABA and the cyclic amino acid GABA uptake inhibitors were, however, less potent than expected. This indicates that the binding site is not identical to, but rather overlapping with, the GABA recognition site of the uptake carrier. The affinity constant for binding of [3H]NO 328 is 18 nM, and the Bmax is 669 pmol/g of original rat forebrain tissue. The regional distribution of NaCl-dependent [3H]NO 328 binding followed that of synaptosomal [3H]GABA uptake.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Determination of delta-aminobutyric acid and other amino acids in cerebrospinal fluid of pediatric patients by reversed-phase liquid chromatography.

The reversed-phase liquid-chromatographic system described here is capable of resolving the neurotransmitter amino acids aspartic acid, glutamic acid, and gamma-aminobutyric acid (GABA) plus 21 other amino acids in cerebrospinal fluid (CSF) in a single analysis. The amino acids, derivatized with o-phthalaldehyde, are separated in 65 min. Concentrations of glutamine less than or equal to 600 mumol/L can be measured at the same time as GABA greater than or equal to 10 nmol/L. Using this method, we have determined reference intervals for amino acids, including GABA, in CSF in a group of pediatric patients who underwent lumbar puncture before myelography, and who were subsequently shown to have normal myelograms. These intervals are generally lower than those previously reported for childhood, but we believe this results from a more rigid selection of the control group. In addition, artifactual increases in concentrations of free neurotransmitters, caused by breakdown of amino acid conjugates, are minimized by (a) immediate freezing of the CSF samples to prevent enzyme-mediated changes, (b) omission of a deproteinization step, and (c) precolumn derivatization to reduce on-column breakdown of amide and peptide forms.

Amino Acids↗
PubMed1993

Effect of a toxin isolated from the sponge Haliclona viridis on the release of gamma-aminobutyric acid from rat olfactory bulb.

A partially purified toxin from the marine sponge Haliclona viridis was studied for its effect on the presynaptic release mechanism of 3H-gamma-aminobutyric acid from nerve terminals of the external plexiform layer of rat olfactory bulb. Previously, the toxin of H. viridis was shown to block the resting potassium conductance in frog muscle. In the present study, the toxin induced a reversible release of 3H-gamma-aminobutyric acid in the external plexiform layer. This effect was similar to that induced by 25 mM K+. The toxin-induced outflow of 3H-gamma-aminobutyric acid was concentration dependent. The action of the toxin was specific for gamma-aminobutyric acid secretion from the external plexiform layer, and dopamine liberation from the frontal cortex; the toxin did not release 3H-valine, a non-neurotransmitter amino acid, from the external plexiform layer. Toxin- and high K(+)-induced neurotransmitter release were both drastically reduced when Ca2+ was removed from the saline. The addition of 0.3 microM tetrodotoxin or the removal of Na+ from the saline did not reduce the toxin's ability to release neurotransmitters. The effect of toxin was enhanced by the addition of valinomycin. Although Haliclona toxin and 4-aminopyridine induced the release of neurotransmitters, they antagonized each other's effect on gamma-aminobutyric acid secretion when added simultaneously.

4-Aminopyridine↗
PubMed2004

The effects of isoflurane on desensitized wild-type and alpha 1(S270H) gamma-aminobutyric acid type A receptors.

UNLABELLED: gamma-aminobutyric acid type A receptors (GABA(A)-R) mediate synaptic inhibition and meet many pharmacological criteria required of important general anesthetic targets. During synaptic transmission GABA release is sufficient to saturate, maximally activate, and transiently desensitize postsynaptic GABA(A)-Rs. The resulting inhibitory postsynaptic currents (IPSCs) are prolonged by volatile anesthetics like isoflurane. We investigated the effects of isoflurane on maximally activated and desensitized GABA(A)-R currents expressed in Xenopus oocytes. Wild-type alpha(1)beta(2) and alpha(1)beta(2)gamma(2s) receptors were exposed to 600 microM GABA until currents reached a steady-state desensitized level. At clinical concentrations (0.02-0.3 mM), isoflurane produced a dose-dependent enhancement of steady-state desensitized current in alpha(1)beta(2) receptors, an effect that was less apparent in receptors including a gamma(2s)-subunit. When serine at position 270 is mutated to histidine (alpha(1)(S270H)) in the second transmembrane segment of the alpha(1)-subunit, the currents evoked by sub-saturating concentrations of GABA became less sensitive to isoflurane enhancement. In addition, isoflurane enhancements of desensitized currents were greatly attenuated by this mutation and were undetectable in alpha(1)(S270H)beta(2)gamma(2s) receptors. In conclusion, isoflurane enhancement of GABA(A)-R currents evoked by saturating concentrations of agonist is subunit-dependent. The effects of isoflurane on desensitized receptors may be partly responsible for the prolongation of IPSCs during anesthesia. IMPLICATIONS: Isoflurane enhances desensitized gamma-aminobutyric acid type A receptor (GABA(A)-R) currents, an effect that is subunit-dependent and attenuated by a mutation in an alpha(1)-subunit pore residue of the GABA(A)-R. As GABA release at inhibitory synapses is typically saturating, isoflurane modulation of desensitized receptors may be partly responsible for prolongation of inhibitory postsynaptic currents during anesthesia.

Anesthetics, Inhalation↗
PubMed1973

Stimulus-coupled secretion of gamma-aminobutyric acid from rat brain synaptosomes.

Synaptosomes treated with radioactive gamma-aminobutyric acid can be stimulated to release this substance. The release is maximal within 40 seconds after stimulation and is dependent on calcium. Magnesium and manganese ions, known to block stimulus-secretion coupling processes, depress calcium-dependent release. This release is specific to synaptosomes because microsomal or myelin fractions do not release accumulated gamma-aminobutyric acid. The data illustrate a simple in vitro system suitable for analysis of secretion of gamma-aminobutyric acid in brain and in addition describe several new aspects of uptake and secretion of this compound at brain nerve endings.

Aminobutyrates↗
PubMed2001

Cycling treatment of anaerobic and aerobic incubation increases the content of gamma-aminobutyric acid in tea shoots.

Gamma-Aminobutyric acid (GABA), a hypotensive compound, is formed from glutamic acid under anaerobic condition in tea shoots. Glutamic acid was exhausted in the first three hours of anaerobic incubation and the increase of GABA stopped. After that, when tea shoots were released under aerobic condition, glutamic acid reproduced rapidly. After one hour of aerobic incubation, tea shoots were given three hours of anaerobic incubation again and then accumulated glutamic acid changed to GABA. The content of GABA increased much more than usual anaerobic incubation. GABA was more in the tea stem than in the leaf.

Aerobiosis↗
PubMed1997

Inhibition of gamma-aminobutyric acid uptake by bicuculline analogues.

Enantiomers of norbicuculline, (+)[1S,9R] and (-)[1R,9S]erythro-1-[1'-(4',5'-methylenedioxyphthalidyl)]-6,7-meth ylenedioxy-1,2,3,4-tetrahydroisoquinoline and of the N-methyl derivatives {(+)[1S,9R] and (-)[1R,9S]bicuculline} were found to inhibit the progress of the gamma-aminobutyric acid transporter-mediated uptake of 40 microM [14C]gamma-aminobutyric acid into native plasma membrane vesicles from the rat cerebral cortex at 30 degrees C. The values for the dissociation constants of the reversible inhibition, relative to (+)[1S,9R]bicuculline, in order of increasing inhibition, were: (-)[1R,9S]bicuculline, 3.3; (+)[1S,9R]-bicuculline, 1.0; (-)[1R,9S]norbicuculline, 0.4 approximately (+)[1S,9R]norbicuculline; guvacine, 0.02. The norbicucullines have higher potencies than (+)[1S,9R]bicuculline for the gamma-aminobutyric acid transporter, in contrast to the relative potencies of these inhibitors for the inhibition of function and gamma-aminobutyric acid binding of the gamma-aminobutyric acid type A receptor.

Animals↗
PubMed1979

Immunocytochemical localization of gamma-aminobutyric acid transaminase at cellular and ultrastructural levels.

gamma-Aminobutyric acid transaminase (GABA-Tase; 4-aminobutyrate:2-oxaglutarate aminotransferase, EC 2.6.1.19) immunoreactivity in the rat's cerebellum was studied by light and electron microscopy with indirect immunofluorescence and peroxidase-antiperoxidase methods. Evidence is presented for neuronal and neuroglial compartments of GABA-Tase. Labeled neurons included stellate, basket, Purkinje, and Golgi cells of the cortex and a few large neurons in the deep nuclei. Labeled neuroglia included those surrounding Purkinje cells, their radial fibers in the molecular layer, and astrocytes in the granular layer and deep nuclei. No evidence for sagittal microzonation was found. At the ultrastructural level, GABA-Tase immunoreactive sites were localized to cell surface membranes, intracellular organelles, and the cytoplasmic matrix. GABA-Tase immunoreactivity at synapses could be localized precisely to pre- and postsynaptic membranes in gamma-aminobutyric acid (GABA)-containing as well as non-GABA-containing neurons. Specific label was absent from tissues treated with normal rabbit preimmune sera. GABA-Tase labeling was more intense in tissues from animals anesthetized with ether than with barbiturates and after formaldehyde fixation without glutaraldehyde. Increased GABA-Tase immunoreactivity was observed on treatment with colchicine, GABA with oxamic acid, GABA, harmaline, norepinephrine and glutamate, or diazepam (in order of decreasing effectiveness). Serotonin produced no detectable change, and apomorphine and muscimol decreased the immunoreactivity.

4-Aminobutyrate Transaminase↗
PubMed1999

Synthesis and characterization of gamma-N-(2-furoylmethyl)aminobutyric acid.

The product of acid hydrolysis of the Amadori compound gamma-N-(1-deoxy-D-fructosyl)aminobutyric acid was isolated and identified by (1)H NMR and (13)C NMR as gamma-N-(2-furoylmethyl)aminobutyric acid. This compound is an analogue to furosine, formed during acid hydrolysis of the corresponding Amadori compound. The retention time of the isolated compound was the same as that of the main peak observed in acid hydrolysates of stored orange juice powder. gamma-N-(2-Furoylmethyl)aminobutyric acid can be a useful indicator of the early stages of Maillard reaction in foods containing free gamma-aminobutyric acid.

Aminobutyrates↗
PubMed1994

Effects of diverse omega-conopeptides on the in vivo release of glutamic and gamma-aminobutyric acids.

omega-Conopeptides are antagonists of subtypes of neuronal calcium channels. Two omega-conopeptides, SVIB and MVIIC, have recently been identified which have a novel specificity for these ionophores. We have tested the actions these peptides, as well as the more selective MVIIA, on the release of glutamic acid and gamma-aminobutyric acid (GABA) in the hippocampus in vivo. For the assay of peptide effects on release, we used microdialysis to deliver multiple pulses of elevated potassium to the brain extracellular fluid. Peptide effects were quantitated from the decrement of the release with peptide perfused through the probes, in comparison to that in control experiments. Synthetic MVIIC caused a 40-50% decrement in the release of both glutamate and GABA at a probe concentration of about 200 nM. Synthetic SVI-B caused a 50% block at about 20-40 microM, while about 200 microM of MVIIA was required for 50% block. Chromatographic experiments showed that differences in potency between MVIIC and MVIIA were not explained by differential degradation. Blockade of release was also observed in the thalamus. MVIIC provides a tool for investigating the role of calcium mediated release of glutamate and GABA in physiological and pathological processes in the mammalian brain in vivo.

Amino Acid Sequence↗