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.

SourceResearch connectionFrom yearThrough year

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

At least 847 records · Page 47Linked to original sources

PubMed1986

Effects of baclofen and gamma-aminobutyric acid on different types of medullary respiratory neurons.

Effects of baclofen and gamma-aminobutyric acid on medullary respiratory neurons were investigated. Medullary inspiratory neurons of the dorsal and ventral respiratory groups were stimulated by baclofen, 0.5-2 mg/kg, and depressed by doses greater than 4-6 mg/kg. Expiratory neurons were depressed by doses of baclofen which increased phrenic nerve activity. Microelectrophoresis of baclofen (5 mM, pH 3) depressed medullary inspiratory neurons. It is suggested that low i.v. doses of baclofen increase inspiratory activity by disinhibition of medullary neurons whereas higher doses directly depress medullary inspiratory neurons.

Animals↗

PubMed2002

[Effect of gamma-aminobutyric acid on the sperm acrosin activity].

OBJECTIVES: To investigate the effect of gamma-aminobutyric acid (GABA) on the sperm acrosin activity in normal men and positive antisperm antibody (AsAb) men. METHODS: Sperm acrosin activity was detected by BAEE/ADH method. RESULTS: GABA could increase the sperm acrosin activity in normal and AsAb positive patients (P < 0.01). The results also indicated that GABA significantly increased Na(+)-K(+)-ATPase activity (P < 0.01), Ca(2+)-ATPase activity (P < 0.05) and SOD activity (P < 0.01) of sperm. CONCLUSIONS: The results demonstrated that GABA could influence the sperm acrosin activity.

Acrosin↗

PubMed1980

Antagonism of some central effects of d-tubocurarine by gamma-aminobutyric acid.

d-Tubocurarine (dtc) administered intracerebroventricularly (icv) to rats produced seizures. Gamma-aminobutyric acid (GABA) administered icv or hydroxylamine administered intraperitoneally (ip) protected the rats from dtc-induced seizures. GABA administered (ip) was ineffective. Local application of dtc to the spinal cord in decerebrate dogs produced facilitation of the scratch reflex. Application of GABA to the spinal cord inhibition the scratch reflex. It is thus concluded that the excitatory effects of dtc on the CNS may be through inhibition of naturally occurring inhibitory substances such as GABA or a closely related compound.

Animals↗

PubMed1978

Purification of an endogenous protein inhibitor of the high affinity binding of gamma-aminobutyric acid to synaptic membranes of rat brain.

In a medium without Na+, gamma-aminobutyric acid (GABA) binds at 0 degrees to freshly prepared crude synaptic membranes from rat cerebral cortex with an apparent dissociation constant of 218 nM. An endogenous inhibitor of the Na+-independent GABA binding was removed from these membranes by freezing and thawing and by repeated washing with Tris citrate buffer (50 mM, pH 7.1) containing 0.01% Triton X-100. As a result, the crude synaptic membranes bind GABA at 0 degrees with two dissociation constants, 20 nM and 111 nM. The endogenous inhibitor is a thermostable (95 degrees for 15 min) acidic protein of approximately 1.5 X 10(4) daltons. It was purified (about 500-fold) with a series of procedures including gel chromatography on Sephadex G-100 and ion exchange chromatography on Dowex 50W-X8 (H+). Recombination of the purified endogenous inhibitor with crude synaptic membrane preparations deprived of the endogenous inhibitor showed that the purified inhibitor blocked noncompetitively the sites for high-affinity GABA binding. A role of this endogenous regulator in the functional of GABA-ergic synapses is discussed.

Animals↗

PubMed1990

CSF gamma-aminobutyric acid in alcoholics and control subjects.

Alcohol has widespread effects on the gamma-aminobutyric acid (GABA) system in the brain. This system in the brain is also postulated to have a role in anxiety, and alcoholics have been reported to have more anxiety disorders. Therefore, the authors undertook a study to compare CSF levels of GABA in abstinent alcoholic patients and normal control subjects. There was no significant difference between groups in CSF levels of GABA. Also, there was no significant difference in GABA level between alcoholic patients with histories of withdrawal seizures and those without such a history.

Adult↗

PubMed1985

Antisera to gamma-aminobutyric acid. II. Immunocytochemical application to the central nervous system.

An antiserum to gamma-aminobutyric acid (GABA) was tested for the localization of GABAergic neurons in the central nervous system using the unlabeled antibody enzyme method under pre- and postembedding conditions. GABA immunostaining was compared with glutamate decarboxylase (GAD) immunoreactivity in the cerebellar cortex and in normal and colchicine-injected neocortex and hippocampus of cat. The types, distribution, and proportion of neurons and nerve terminals stained with either sera showed good agreement in all areas. Colchicine treatment had little effect on the density of GABA-immunoreactive cells but increased the number of GAD-positive cells to the level of GABA-positive neurons in normal tissue. GABA immunoreactivity was abolished by solid phase adsorption to GABA and it was attenuated by adsorption to beta-alanine or gamma-amino-beta-hydroxybutyric acid, but without selective loss of immunostaining. Reactivity was not affected by adsorption to glutamate, aspartate, taurine, glycine, cholecystokinin, or bovine serum albumin. The concentration (0.05-2.5%) of glutaraldehyde in the fixative was not critical. The antiserum allows the demonstration of immunoreactive GABA in neurons containing other neuroactive substances; cholecystokinin and GABA immunoreactivities have been shown in the same neurons of the hippocampus. In conclusion, antisera to GABA are good markers for the localization of GABAergic neuronal circuits.

Adsorption↗

PubMed1991

Sleep promoting effect of a putative glial gamma-aminobutyric acid uptake blocker applied in the thalamus of cats.

The uptake of gamma-aminobutyric acid (GABA) by glial cells was decreased when 4,5,6,7,-tetrahydroisoxazolo-(4,5-C)-pyridin-3-ol (THPO) was applied in the thalamus of freely moving cats by in vivo microdialysis. A marked reduction in duration of wakefulness and in number of awakenings was obtained during THPO treatment. THPO did not change the ratio of slow-wave-sleep and paradoxical sleep but only increased the total sleep time. The present data suggest a possible regulatory role of the glial-neuronal interaction in the modification of the sleep-waking cycle.

Animals↗

PubMedDate not supplied

Gamma-aminobutyric acid and bicuculline effects on acetylcholine metabolism in the striatum in rats.

Gamma-aminobutyric acid (GABA) injected into the lateral ventricles of rat bran in a dose of 600 microgram raised the level and increased the synthesis of acetylcholine (ACh) raising also the activity of choline acetyltransferase (ChAc) but had no effect on the activity of cholinesterase (AChE) in rat striatum. Bucuculline (Bk) in doses of 10 mirogram i.c.v reduced ACh synthesis and in 50 and 10 microgram doses reduced the activity of ChAc. No Bk effect on AChE activity was demonstrated. The observed effects of GABA were abolished by pretreatment with Bk in doses of 1, 5 or 10 microgram.

Acetylcholine↗

PubMed1985

Synaptic inhibition and cell communication; impairment of cell-to-cell coupling produced by gamma-aminobutyric acid (GABA) in the somatic musculature of Ascaris lumbricoides.

The influence of gamma-aminobutyric acid (GABA) (10(-5) M) on the electrical coupling of giant somatic muscle cells of Ascaris lumbricoides was investigated. GABA enhanced the resting potential of the cells and abolished the spike activity. The coupling coefficient (V2/V1) was reduced by 58.8% while the input resistance (Rin) was decreased by 38.8%. The decline in Rin was not related to unlinearity of the current-voltage relation. As the time constant of cell membrane was reduced by 28.4% by the addition of GABA the effect of the neurotransmitter on cell-to-cell coupling seems to be mainly related to a decrease in resistance of the non-junctional membrane due to an increase in chloride conductance.

Action Potentials↗

PubMed1980

[Effect of gamma-aminobutyric acid and its analogs on the smooth muscle of veins].

Effect of gamma-aminobutyric acid (GABA) and its agonists, phenibut, phenylpyrrolidone and LGPI-29, on contractility of smooth muscle cells was studied on an isolated rat vena porta. The contractility was recorded by a rapidly operating 6MH-1B mechanotrone to show that the solutions of GABA and those of phenibut (to a less extent) exert a distinct inhibitory effect on smooth muscle cells of the rat vena porta at a concentration of 10--20 mM. Phenylpyrrolidone and LGPI-29 did not decrease vascular tone. Depolarization of the cell membrane did not interfere with the inhibitory effect of GABA and its agonists on smooth muscle cell contractility of the rat vena porta.

Animals↗

PubMed2003

Inhibition of acute hyperammonemia-induced convulsions by systemically administered gamma aminobutyric acid in rats.

The present study has investigated the effects of intraperitoneally administered gamma aminobutyric acid (GABA) on ammonium chloride-induced hyperammonemia and convulsions in rats. Systemically administered GABA did not alter the concentration of GABA in the brain of control as well as hyperammonemic animals. However, hyperammonemia-induced convulsions were inhibited by GABA in a dose-dependent manner. This was accompanied by a dose-dependent decrease in the concentrations of ammonia in both blood and brain and an elevation of glutamine in the blood. These results suggest that GABA has the potential to prevent acute hyperammonemia by increasing detoxification of ammonia to glutamine. As a result, the diffusion of ammonia from blood into the brain has been decreased. This accounts for an inhibition of convulsions by systemically administered GABA in hyperammonemic animals.

Ammonia↗

PubMed1987

Modulation of gamma-[3H]aminobutyric acid release from rat cortical slices by alpha 2-adrenoceptors.

Modulation of gamma-aminobutyric acid (GABA) release by alpha 2-adrenoceptor agonists has not been consistently demonstrated. This could be due to high levels of norepinephrine (NE) concomitantly evoked by stimulation parameters needed for GABA release. In the present experiments, NE release was preferentially decreased by omission of calcium (Ca2+) and alpha 2-modulation of [3H]GABA release from cortical slices was measured. The antagonist rauwolscine increased only Ca2+-dependent [3H]GABA release, while the agonists guanabenz and clonidine inhibited only Ca2+-independent GABA release. These results suggest that release of endogenous NE diminished the effect of alpha 2-agonists but reveals the effect of antagonists and support the hypothesis that endogenous NE inhibits GABA release in cortex.

Animals↗

PubMed2004

Ethanol regulation of gamma-aminobutyric acid A receptors: genomic and nongenomic mechanisms.

gamma-Aminobutyric acid(A) (GABA(A)) receptors are ligand-gated ion channels that, predominantly, mediate inhibitory synaptic transmission in the CNS. These receptors are pentameric complexes that are comprised of subunits from several classes (alpha, beta, gamma, delta, ), with each class consisting of several isoforms. Chronic ethanol consumption alters GABA(A) receptor function producing cellular tolerance to GABA and ethanol, cross-tolerance to benzodiazepines and barbiturates, and sensitization to inverse agonists. Recent studies have clearly demonstrated that GABA(A) receptors play an important role in ethanol dependence and functional properties of GABA(A) receptor are altered following chronic ethanol administration. However, the exact mechanisms that account for alterations in GABA(A) receptor function following chronic ethanol administration have not been resolved. The mechanisms responsible for adaptation of GABA(A) receptors to chronic ethanol exposure may involve ethanol-induced changes in cell surface expression, subcellular localization, synaptic localization, receptor phosphorylation, neurosteroids, and/or changes in GABA(A) receptor subunit composition. In this review, we provide an overview of recent data pertaining to mechanisms that could be responsible for altered properties and expression of GABA(A) receptors following chronic ethanol administration.

Alcoholism↗

PubMed1998

Anesthesia sensitivity in mice that lack the beta3 subunit of the gamma-aminobutyric acid type A receptor.

BACKGROUND: The mammalian gamma-aminobutyric acid type A (GABA(A)) receptor, a likely target of anesthetic action, exhibits remarkable subunit heterogeneity. In vitro expression studies suggest that there is subunit specificity to anesthetic responses at the GABA(A) receptor. The authors tested whether genetically engineered mice that lack the beta3 subunit of the GABA(A) receptor differed in their sensitivities to several general anesthetic agents. METHODS: Median effective concentrations for loss-of-righting reflex and tail clamp/withdrawal for enflurane and halothane were determined in mice with and without the beta3 gene and gene product. Sleep time was measured after intraperitoneal injection of pentobarbital, ethanol, etomidate, and midazolam. RESULTS: Null allele mice (beta3 -/-) did not differ from wild-type mice (beta3 +/+) in the obtunding response to enflurane and halothane but were significantly more resistant to enflurane (null allele half-effect concentrations [EC50] of 2.59 +/- 0.10 vs. wild-type EC50 of 2.06 +/- 0.12 atm %, P < 0.001) and halothane (null allele EC50 of 1.73 +/- 0.04 vs. wild-type EC50 of 1.59 +/- 0.05 atm %, P = 0.01) as determined by tail clamp response. Wild-type and null allele mice exhibited divergent responses to other sedative agents active at the GABA(A) receptor. No differences were noted in sleep times after administration of pentobarbital and ethanol, but null allele mice were more resistant to etomidate (null allele EC50 of 17.8 +/- 1.9 min vs. wild-type EC50 of 26.2 +/- 2.4 min, P < 0.02) and midazolam (null allele EC50 of 14.2 +/- 7.8 min vs. wild-type EC50 of 41.3 +/- 10.4 min, P < 0.05). CONCLUSIONS: The beta3 subunit of the GABA(A) receptor appears to be important in the mediation of the immobilizing (tail clamp) but not obtunding (loss-of-righting reflex) effects of the volatile anesthetic agents enflurane and halothane. These data support the hypotheses that separate components of the anesthetic state are mediated via different central nervous system loci; that the GABA(A) receptor is a likely target for the immobilizing response to volatile anesthetic agents; and that the beta3 subunit plays a direct or indirect role in the mediation of this response. Absence of the beta3 subunit appears to attenuate the obtunding effect of midazolam and etomidate but appears not to alter the obtunding effect of pentobarbital, enflurane, and halothane, suggesting that these anesthetic agents produce hypnosis by different specific molecular mechanisms.

Anesthetics, General↗

PubMed1994

The Synthesis of [gamma]-Aminobutyric Acid in Response to Treatments Reducing Cytosolic pH.

[gamma]-Aminobutyric acid (GABA) synthesis (L-glutamic acid + H+ -> GABA + CO2) is rapidly stimulated by a variety of stress conditions including hypoxia. Recent literature suggests that GABA production and concomitant H+ consumption ameliorates the cytosolic acidification associated with hypoxia or other stresses. This proposal was investigated using isolated asparagus (Asparagus sprengeri Regel) mesophyll cells. Cell acidification was promoted using hypoxia, H+/L-glutamic acid symport, and addition of butyrate or other permeant weak acids. Sixty minutes of all three treatments stimulated the levels of both intracellular and extracellular GABA by values ranging from 100 to 1800%. At an external pH of 5.0, addition of 5 mM butyrate stimulated an increase in overall GABA level from 3.86 (0.56 [plus or minus] SE) to 20.4 (2.16 [plus or minus] SE) nmol of GABA/106 cell. Butyrate stimulated GABA levels by 200 to 300% within 15 s, and extracellular GABA was observed after 10 min. The acid load due to butyrate addition was assayed by measuring [14C]butyrate uptake. After 45 s of butyrate treatment, H+-consuming GABA production accounted for 45% of the imposed acid load. The cytosolic location of a fluorescent pH probe was confirmed using fluorescent microscopy. Spectrofluorimetry indicated that butyrate addition reduced cytosolic pH by 0.60 units with a half-time of approximately 2 s. The proposal that GABA synthesis ameliorates cytosolic acidification is supported by the data. The possible roles of H+ and Ca2+ in stimulating GABA synthesis are discussed.

Journal Article↗

PubMed1986

Effects of gamma-aminobutyric acid on cones and bipolar cells of the tiger salamander retina.

The gamma-aminobutyric acid (GABA) system in the tiger salamander retina was studied using autoradiographic and electrophysiological techniques. A high-affinity uptake mechanism for GABA has been localized in about 60% of the horizontal cells and about 30% of the amacrine cells. Effects of exogeneously applied GABA on the membrane conductance of cones and hyperpolarizing bipolar cells (HBC) were examined using the two electrode current-clamp technique in the living retinal slices. In both cell types, 1 mM of GABA caused a conductance increase. In perfused eyecups, 2 mM of GABA selectivity abolished the surround response of the HBC and left the center response unchanged. These results are consistent with the notion that a population of horizontal cells and a population of amacrine cells in the salamander retina may use GABA as their neurotransmitter.

Ambystoma↗

PubMed1985

Elevated serum gamma-aminobutyric acid levels in children with Reye's syndrome.

Elevated serum levels of gamma-aminobutyric acid (GABA), a potent inhibitory neurotransmitter, have recently been implicated in the pathogenesis of hepatic encephalopathy. In this study, serum GABA levels were measured in five children with severe Reye's syndrome, 10 children with acute viral hepatitis, and seven healthy volunteers. Serum GABA levels were highest in the five Reye's syndrome patients. The mean serum GABA level for the Reye's syndrome group (3.0 +/- 1.3 microM, mean +/- SEM) was significantly elevated as compared to the mean of the viral hepatitis group (0.72 +/- 0.07 microM, p less than 0.05) and the healthy volunteers (0.38 +/- 0.04 microM, p less than 0.05). These results provide preliminary evidence to suggest that elevated serum GABA levels may in part be responsible for the encephalopathic state observed in children with Reye's syndrome.

Child↗

PubMed1997

Analogues of gamma-aminobutyric acid (GABA) and trans-4-aminocrotonic acid (TACA) substituted in the 2 position as GABAC receptor antagonists.

1. gamma-Aminobutyric acid (GABA) and trans-4-aminocrotonic acid (TACA) have been shown to activate GABAC receptors. In this study, a range of C2, C3, C4 and N-substituted GABA and TACA analogues were examined for activity at GABAC receptors. 2. The effects of these compounds were examined by use of electrophysiological recording from Xenopus oocytes expressing the human rho 1 subunit of GABAC receptors with the two-electrode voltage-clamp method. 3. trans-4-Amino-2-fluorobut-2-enoic acid was found to be a potent agonist (KD = 2.43 microM). In contrast, trans-4-amino-2-methylbut-2-enoic acid was found to be a moderately potent antagonist (IC50 = 31.0 microM and KB = 45.5 microM). These observations highlight the possibility that subtle structural substitutions may change an agonist into an antagonist. 4. 4-Amino-2-methylbutanoic acid (KD = 189 microM), 4-amino-2-methylenebutanoic acid (KD = 182 microM) and 4-amino-2-chlorobutanoic acid (KD = 285 microM) were weak partial agonists. The intrinsic activities of these compounds were 12.1%, 4.4% and 5.2% of the maximal response of GABA, respectively. These compounds more effectively blocked the effects of the agonist, GABA, giving rise to KB values of 53 microM and 101 microM, respectively. 5. The sulphinic acid analogue of GABA, homohypotaurine, was found to be a potent partial agonist (KD = 4.59 microM, intrinsic activity 69%). 6. It was concluded that substitution of a methyl or a halo group in the C2 position of GABA or TACA is tolerated at GABAC receptors. However, there was dramatic loss of activity when these groups were substituted at the C3, C4 and nitrogen positions of GABA and TACA. 7. Molecular modelling studies on a range of active and inactive compounds indicated that the agonist/competitive antagonist binding site of the GABAC receptor may be smaller than that of the GABAA and GABAB receptors. It is suggested that only compounds that can attain relatively flat conformations may bind to the GABAC receptor agonist/competitive antagonist binding site.

Animals↗