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 1,747 records · Page 97Linked to original sources
PubMed1982

Serotonin and gamma-aminobutyric acid turnover after injection into the median raphe of substance P and D-ala-met-enkephalin amide.

The raphe nuclei [which contain serotonin (5-HT) cell bodies] are also known to contain axons that store substance P, met-enkephalin, and gamma-aminobutyric acid (GABA). We have previously shown that GABA has a tonic inhibitory action on 5-HT turnover. To examine other possible interactions of these neuronal systems, we assessed the effect on 5-HT turnover of injecting substance P and 2-D-ala-met-enkephalin into the median raphe nucleus, and the effects of substance P on GABA turnover. Serotonin turnover was increased by 30% in the hippocampus after the injection of substance P (4 micrograms) into the median raphe, indicating an excitatory effect of substance P on the raphe-hippocampal system. Local injection of the metabolically stable metenkephalin analog 2-D-ala-met-enkephalin amide (10 micrograms) increased the hippocampal steady state content of 5-hydroxyindoleacetic acid (5-HIAA) by 60%. The data suggest an excitatory effect of met-enkephalin within the raphe nucleus. We attempted to estimate GABA turnover from the rate of disappearance of GABA after inhibition of glutamic acid decarboxylase by isoniazid and by the rate of accumulation of GABA after inhibition of GABA transaminase by gabaculine. Isoniazid, which is a competitive inhibitor, had too short and incomplete an action to be of use when injected intranuclearly. Gabaculine, which is an irreversible inhibitor, induced a rapid-onset increase in GABA content. This accumulation was linear up to 90 min. The injection fo gabaculine (80 ng) into the raphe increased GABA content by five times the control values, but hippocampal 5-HT and 5-HIAA contents were not significantly changed. Substance P injection increased the GABA turnover by 30%. Gabaculine seems a promising tool for detecting changes in GABA turnover.

Animals↗
PubMed1997

Effects of rat galanin and galanin message associated peptide (GMAP) on rat growth hormone secretion and stimulating effect of gamma-aminobutyric acid on galanin release from rat hypothalamus.

Immunoreactive galanin and galanin message associated peptide (GMAP) were detectable in rat hypothalamus in the concentration of 563 +/- 23 and 14.3 +/- 3.1 fmol/hypothalamus, respectively. gamma-Aminobutyric acid (GABA) elicited a dose-related increase in galanin release from rat hypothalamic fragments, which was inhibited by picrotoxin, a GABA antagonist. Growth hormone (GH) secretion from rat anterior pituitary cells were stimulated by rat galanin, but not by GMAP. These findings suggest that hypothalamic galanin, but not GMAP, may play roles in GH secretion induced by GABAergic mechanisms in the rat.

Analysis of Variance↗
PubMed1987

gamma-Aminobutyric acid as an inhibitory neurotransmitter in the rat supraoptic nucleus: intracellular recordings in the hypothalamic slice.

Intracellular recordings have been made from rat supraoptic neurones in the hypothalamic slice preparation. Application of gamma-aminobutyric acid (GABA) caused all neurones to hyperpolarise and this was accompanied by an increase in membrane conductance. GABA application examined on a variety of cells was found to have a potent influence on patterning of electrical activity, always consistent with an inhibitory action.

Acetylcholine↗
PubMed1991

Inhibition of high-affinity gamma-aminobutyric acid uptake in primary astrocyte cultures by phorbol esters and phospholipase C.

The effects of phorbol 12-myristate 13-acetate (PMA), a potent activator of protein kinase C (PKC), on high-affinity Na(+)-dependent gamma-aminobutyric acid (GABA) uptake were investigated in primary cultures of neurons and glial cells from rat brain cortex. Incubation of glial cells with PMA led to concentration- and time-dependent decreases in the GABA transport in glial cells. This effect could be completely suppressed by addition of the PKC inhibitor H7. The PMA effects could be mimicked by oleoylacetylglycerol, the diacylglycerol kinase inhibitor R59022 and exogenous phospholipase C. Treatment with PMA did not affect GABA transport in neuronal cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMedDate not supplied

Usefulness of gamma-aminobutyric acid (GABA) therapy in pathologies of neurosurgical competence.

The Authors, after giving some theoretical and pharmacodynamic opinions on GABA, report their clinical experience for 18 consecutive years with the use of gamma-aminobutyric acid in cases of central comas, psycho-organic post-operative syndromes, Parkinson's Disease. The drug, in the various above listed pathologies, shows respectively a wakening effect, with actual rising of the level of consciousness, a re-equilibrating action towards psycho-organic involutions, especially acute ones, and a considerable antiakinetic activity. After analyzing the original results obtained, considered especially in the light of the most modern researches on the importance of GABA-ergic mediation on the basal ganglia, some interesting neurofunctional hypotheses are put forward, which are connected with the problem of nervous conduction in human pathology. According to said hypotheses the aminoacid works clinically, owing to its role of inhibiting mediator (rather than of oxidable substrata), and is involved in extrapyramidal nigro-striatal lesions.

Aged↗
PubMedDate not supplied

[Anti-ulcer effect of gamma-aminobutyric acid and its mechanisms of action].

It has been shown in experiments on white rats with chronic gastric ulcer induced according to the method of Takashi and coworkers that intramuscular administration of gamma-aminobutyric acid (GABA) exerts a pronounced antiulcerous effect. As compared with ganglerone, GABA reduces the content of free physiologically active histamine in the gastric mucosa to a far greater extent. The relationship has been disclosed between the therapeutic effect of GABA and the decreased content of histamine in the gastric mucosa.

Animals↗
PubMed1970

The metabolism of gamma aminobutyric acid in the lobster nervous system. Enzymes in single excitatory and inhibitory axons.

gamma-aminobutyric acid (GABA) is the inhibitory transmitter compound at the lobster neuromuscular junction. This paper presents a comparison of the enzymes of GABA metabolism in single identified inhibitory and excitatory axons from lobster walking legs. Inhibitory axons contain more than 100 times as much glutamic decarboxylase activity as do excitatory axons. GABA-glutamic transaminase is found in both excitatory and inhibitory axons, but about 50% more enzyme is present in inhibitory axons. The kinetic and electrophoretic behavior of the transaminase activity in excitatory and inhibitory axons is similar. Succinic semialdehyde dehydrogenase is found in both axon types, as is an unknown enzyme which converts a contaminant in radioactive glutamic acid to GABA. In lobster inhibitory neurons, therefore, the ability to accumulate GABA ultimately rests on the ability of the neuron to accumulate the enzyme glutamic decarboxylase.

Aminobutyrates↗
PubMed1997

A single dose of methamphetamine in neonatal gerbils affects adult prefrontal gamma-aminobutyric acid innervation.

A single non-invasive dose of methamphetamine (50 mg/kg i.p.) was administered to neonatal male gerbils (Meriones unguiculatus) aged 14 days. At the age of postnatal day 90, the gamma-aminobutyric acid (GABA) immunoreactive profiles were electron microscopically quantified in the prelimbic area of the prefrontal cortex and compared with those of saline-treated controls. This early solitary drug challenge resulted in adult GABAergic innervation densities which were approximately 40% above those of saline-treated controls.

Animals↗
PubMed1994

Immunohistochemical and histochemical evidence for the presence of noradrenaline, serotonin and gamma-aminobutyric acid in chief cells of the mouse carotid body.

The immunohistochemical study revealed tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), phenylethanolamine N-methyltransferase (PNMT), serotonin, glutamate decarboxylase (GAD) and gamma-aminobutyric acid (GABA) immunoreactivities in the mouse carotid body. TH and DBH immunoreactivities were found in almost all chief cells and a few ganglion cells, and in relatively numerous varicose nerve fibers of the carotid body. The histofluorescence microscopy showed catecholamine fluorescence in almost all chief cells. However, no PNMT immunoreactivity was observed in the carotid body. Serotonin, GAD and GABA immunoreactivities were also seen in almost all chief cells of the carotid body. From combined immunohistochemistry and fluorescence histochemistry, catecholamine and serotonin or catecholamine and GABA were colocalized in almost all chief cells. Thus, these findings suggest that noradrenaline, serotonin and GABA may be synthesized and co-exist in almost all chief cells of the mouse carotid body and may play roles in chemoreceptive functions.

Animals↗
PubMed1991

(-)-baclofen and gamma-aminobutyric acid inhibit calcium currents in isolated retinal ganglion cells.

Of the various synaptic inputs known to converge upon retinal ganglion cells, the major inhibitory inputs are thought to be GABAergic. Although gamma-aminobutyric acid (GABA) is known to activate anion-selective ion channels in retinal ganglion cells, we have tested the possibility that GABA can also modulate cationic conductances in these cells, as seen in other central and peripheral neurons. Specifically, we have made whole-cell patch-clamp recordings to test whether voltage-gated calcium currents in isolated goldfish retinal ganglion cells are sensitive to GABAB receptor ligands. (-)-Baclofen and GABA inhibited calcium currents activated by moderately long depolarizations and, during large depolarizations (e.g., to 0 mV), also appeared to accelerate the rate of current decay. The calcium current inhibition induced by (-)-baclofen and GABA was not prevented by 2-hydroxysaclofen, phaclofen, or bicuculline, even though bicuculline suppressed a GABA-activated conductance in these cells. These results demonstrate the presence of baclofen- and GABA-sensitive calcium currents in vertebrate retinal ganglion cells as well as the coexistence of GABAA and GABAB receptors in individual retinal ganglion cells.

Animals↗
PubMed1983

Role of K+ in GABA (gamma-aminobutyric acid)-evoked depolarization of peripheral nerve.

Isolated, desheathed sciatic nerves of the leopard frog or bull frog were used in studies to determine different sources/components of the depolarizing effect of GABA (gamma-aminobutyric acid) on myelinated fibers. During the depolarization induced by 1 mM GABA--which was reflected by an increase of 38.3% (S.E. +/- 2.2) in the amplitude of the evoked half-maximal A-fiber compound action potential--the level of extracellular potassium ([K+]o) measured at depths less than or equal to 200 microns in the nerve with ion-selective microelectrodes, increased by 0.096 mM (S.E. +/- 0.007). Changes in excitability preceded K+]o, and there was a significant difference between their peak latencies. Artificially raised levels of [K+]o, similar to those induced by GABA, caused extremely small changes (less than 10%) in the size of the evoked action potential. From the magnitude and time course of the GABA-evoked augmentation of levels of [K+]o, it can be concluded that potassium ions probably arise indirectly and play a secondary role in what appears to be a mainly receptor-mediated depolarization of axons. A much greater sensitivity to GABA was found for fibers of the dorsal roots in comparison with those of the ventral roots (maximal changes in excitability of 50% and 6% respectively). This suggests that the depolarization of ventral root fibers could be caused by [K+]o accumulation, and that there may be a preferentially localized distribution of receptors for GABA on the sensory axons of peripheral nerve.

Animals↗
PubMed1983

Effect of dopamine agonists on gamma-aminobutyric acid (GABA) turnover in the superior colliculus: evidence that nigrotectal GABA projections are under the influence of dopaminergic transmission.

The effect of dopamine (DA)-mimetic drugs on the turnover rate of gamma-aminobutyric acid (GABA) in the superficial and deep layers of superior colliculus (SC) was studied. As an index of GABA turnover, the rate of accumulation of GABA was measured after irreversible inhibition of GABA-transaminase by gamma-vinyl-GABA, microinjected directly into SC. The rate of GABA accumulation in the deep layers of SC decreased by 30 to 45% after systemic administration of apomorphine, amphetamine and cocaine. This effect of DA agonists was prevented by pretreatment with haloperidol. A similar decrease in the rate of GABA accumulation in the deep layers of SC was observed after microinjection of the GABA agonist, muscimol (0.4 nmol) directly into the substantia nigra. Nigral microinjection of the GABA antagonist bicuculline (1.0 nmol), which per se did not affect GABA accumulation in SC, antagonized the effect of apomorphine on GABA accumulation in the deep layers of SC. The results indicate that the nigrotectal GABAergic pathway which terminates in the deep layers of SC is subject to regulation by DA transmission. Furthermore, the effect of DA agonists on tectal GABA turnover is mediated via GABA release in SN. In the superficial layers of SC a small but significant decrease in GABA turnover was observed after apomorphine. In contrast to the effects observed in the deep layers of SC, this effect was not dependent on GABAergic transmission in substantia nigra, but was dependent upon the integrity of visual pathways.

Animals↗
PubMed1983

Modulation of cortical acetylcholine and gamma-aminobutyric acid release in freely moving guinea pigs: effects of clonidine and other adrenergic drugs.

The effects of various doses of clonidine and norepinephrine (NE) on the release of acetylcholine (ACh) and gamma-aminobutyric acid (GABA) from the brain surface of freely moving guinea pigs have been investigated in order to study the role of alpha adrenoceptors on the function of cortical cholinergic and GABAergic neurons. Clonidine administration at doses of 7.5 and 18.7 nmol/kg inhibits by 40% the release of ACh; larger doses (112 nmol/kg) are inactive. On the other hand, the largest dose of clonidine used in this study (112 nmol/kg) increases the release of GABA by 45%, whereas lower doses are inactive. Norepinephrine (0.9 mumol i.c.v.) decreases by 40% the release of ACh and increases by 80% that of GABA. The inhibitory effects of clonidine and of NE on cortical ACh output are completely antagonized by yohimbine (0.28 mumol/kg), a selective alpha-2 antagonist, thus suggesting an involvement of the alpha-2 adrenoceptors in the neurochemical action of the drug. However, yohimbine releases GABA and does not prevent the action of clonidine or of NE on the cortical GABA system. On the other hand, prazosin (35.8 nmol/kg), a selective alpha-1 antagonist, completely antagonizes the stimulating effects of clonidine and of NE on the release of GABA, suggesting that alpha-1 receptors modulate this release. The present experiments indicate that the neurochemical and neuropharmacological profile of activity of clonidine is strictly dependent upon the dose of the drug. In addition, they support the concept that cortical alpha adrenoceptors modulate the function of neurons releasing ACh or GABA.

Acetylcholine↗
PubMed1989

Reduction of highly elevated plasma levels of gamma-aminobutyric acid does not reverse hepatic coma.

The pathogenesis of coma in patients with fulminant hepatic failure is still unknown, but there is some evidence that decreased hepatic metabolism of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) may be involved. If this hypothesis is true, reduction of increased GABA levels in patients with hepatic encephalopathy should reduce the depth of hepatic coma. In the case described here, highly elevated plasma GABA levels were reduced by cross-circulation with baboon liver. No amelioration of the coma was observed, thus suggesting that decreased hepatic metabolism of GABA is not critically involved in hepatic encephalopathy.

Adult↗
PubMed1999

Immunoelectron microscopic study of gamma-aminobutyric acid inputs to identified thalamocortical projection neurons in the anterior thalamus of the rat.

We have carried out a semi-quantitative ultrastructural study to determine the characteristics and distribution of gamma-aminobutyric acid (GABA)-containing constituents of the anterodorsal (AD) and anteroventral (AV) thalamic nuclei in adult rats. We used a polyclonal antibody to GABA and a postembedding immunogold detection method in animals in which the cortical projection neurons of these nuclei had been labelled by retrograde transport of cholera toxin/horseradish peroxidase (HRP) injected into the retrosplenial granular cortex. Two types of GABA-immunopositive structures were identified, with gold particle densities 4-40 times higher than the highest densities over blood-vessel lumens and areas of empty resin: (1) an apparently homogeneous population of axon terminals with Gray type-2 (symmetric) synaptic contacts corresponding to F-axon terminals; and (2) small-medium sized myelinated axons scattered individually or in small groups within the neuropil which may be their parent axons. These axons and terminals may originate from the ipsilateral thalamic reticular nucleus; others may arise from the basal forebrain or brainstem. The GABA-immunopositive terminals comprised approximately 16% of all axon terminal profiles in AD and 12% in AV, a significant difference. However, because the immunoreactive axon terminals in AD were significantly larger than those in AV (1.09+/-0.47 microm2 vs 0.90+/-0.43 microm2) and would therefore be encountered more frequently, it is not possible to conclude that the GABAergic innervation of AD is heavier than that of AV. The GABA-positive terminals established synaptic contacts with cell bodies and dendrites of all sizes (some of which were HRP-labelled) with the following frequency distribution (AD/AV, no significant difference): somata 5%/7%; large dendrites (> or = 1.5 microm) 14%/9%; medium dendrites (1.00-1.49 microm) 35%/45% and small dendrites (< 1 microm) 46%/40%. Despite evidence from previous studies, we found no evidence in this study for the presence of GABAergic interneurons or for GABA-containing projection neurons in AD or AV.

Animals↗
PubMed1984

Comparison of norepinephrine- and benzodiazepine-induced augmentation of Purkinje cell responses to gamma-aminobutyric acid (GABA).

The hypothesis tested in the present study was that the benzodiazepines (i.e., flurazepam) and norepinephrine (NE) share a common mechanism to facilitate cerebellar Purkinje neuron responsiveness to iontophoretically applied gamma-aminobutyric acid (GABA). Extracellular activity was recorded from Purkinje neurons in halothane-anesthetized rats from each of the following groups: 1) naive, 2) acute or chronic flurazepam treated, 3) chronic desmethylimipramine treated and 4) injected with 6-hydroxydopamine. Single unit responses to pulsatile (10 sec duration at 45-sec intervals) iontophoretic administration of GABA were examined before, during and after NE or flurazepam microiontophoresis in all treatment groups. Drug response histograms were generated and used to quantitate NE and flurazepam effects on spontaneous activity and GABA-induced inhibitory responses. Doses of GABA sufficient to produce depression of Purkinje cell activity in naive rats (4-40 nA) suppressed firing rate in all Purkinje cells tested in drug-treated animals. In contrast to its consistent GABA facilitating action in naive controls, iontophoretically applied flurazepam was ineffective in augmenting GABA-induced suppression of Purkinje cell discharge in acute and chronic flurazepam-treated animals. Although GABA facilitation by NE was unaffected by acute systemic administration of a benzodiazepine, chronic treatment with flurazepam produced a subsensitivity to the noradrenergic GABA facilitating effects. Within 48 hr of withdrawal from chronic benzodiazepine treatment, both NE and flurazepam again enhanced GABA-induced suppression of Purkinje cell discharge routinely. Chronic desmethylimipramine treatment as well as iontophoresis of the blocking agents sotalol and fluphenazine which have been shown previously to block or reduce NE-mediated enhancement of GABA actions were ineffective in altering the facilitating effect of flurazepam on GABA. Likewise, 6-hydroxydopamine pretreatment had no effect on GABA augmentation by flurazepam. Thus, although flurazepam appears to act independently from the noradrenergic receptor system in augmenting GABA-induced depression of Purkinje cell discharge, a reversible subsensitivity to the GABA facilitating effects of both flurazepam and NE can be produced by chronic treatment with this benzodiazepine. On the basis of this "cross-subsensitivity" to NE and flurazepam actions, it seems reasonable to suggest that these two agents might enhance GABA inhibitory actions by a common biophysical mechanism subsequent to noradrenergic receptor activation.

Animals↗
PubMed2000

Ethanol modulation of gamma-aminobutyric acid (GABA)-mediated inhibition of cerebellar Purkinje neurons: relationship to GABAb receptor input.

BACKGROUND: Electrophysiological recording reveals that only a portion of cerebellar Purkinje neurons are sensitive to ethanol enhancement of gamma-aminobutyric acid (GABA) responses. Although activation of beta-adrenergic receptors permits ethanol enhancement of GABA function from some cerebellar Purkinje neurons, other neurons remain insensitive to ethanol. These findings are consistent with the finding that other external neural inputs are required to allow ethanol enhancement of GABA responses from Purkinje neurons. Because of a high expression of GABA(B) receptors on Purkinje cells, we tested whether activation of GABA(B) receptors might modulate the action of ethanol on GABA responsiveness. METHODS: Extracellular single-unit electrophysiological recording was used to investigate the effects of ethanol on responses to GABA and muscimol (a GABA(A) agonist) from cerebellar Purkinje neurons. Drugs tested were baclophen (a GABA(B) agonist) and CGP35348 (a GABA(B) antagonist). RESULTS: Ethanol did not enhance responses to GABA and muscimol from all Purkinje neurons. Systemic administration of the GABA(B) agonist, baclophen (3 mg/kg intravenously), permitted ethanol to enhance GABA inhibition from approximately 75% of cerebellar Purkinje neurons not initially enhanced by ethanol. Local iontophoretic application of baclophen to Purkinje neurons also allowed ethanol to enhance GABA and muscimol responsiveness from a portion of neurons in which ethanol initially did not affect their actions. An inhibitory action of ethanol on responses to GABA and muscimol, which was also influenced by baclophen, was observed from some Purkinje neurons. From Purkinje neurons initially sensitive to ethanol enhancement of GABA and muscimol function, administration of CGP35348, a GABA(B) antagonist, diminished the effect of ethanol on the responsiveness of these agonists from the majority (9/15) of neurons. CONCLUSIONS: The present findings demonstrated that baclophen allows ethanol enhancement of GABA and muscimol responsiveness from some, but not all, cerebellar Purkinje neurons initially not sensitive to ethanol. Likewise, a GABA(B) antagonist can diminish ethanol enhancement of GABA and muscimol responses from some ethanol-sensitive neurons. Thus, these results emphasize that GABA(B) receptors on a portion of Purkinje neurons act as an auxiliary neural input that allows ethanol enhancement of GABA responses. Consequently, receptor structure alone does not account for the action of ethanol on GABA(A) receptor function on this cell type.

Animals↗