PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “GABA”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

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

At least 19 recordsLinked to original sources
PubMed1977

Audiogenic seizure protection by elevated brain GABA concentration in mice: effects of gamma-acetylenic gaba and gamma-vinyl GABA, two irreversible GABA-T inhibitors.

gamma-Acetylenic GABA and gamma-vinyl GABA, two catalytic irreversible inhibitors of GABA-transaminase, produce marked and sustained elevations in mouse brain GABA concentrations and protect DBA/2 mice against audiogenically induced seizures in a similar dose and time-dependent manner. The acetylenic analog also inhibits GAD activity while the vinyl compound has minimal activity against this enzyme. The increase in brain GABA concentrations induced by these compounds correlates well with attenuation of audiogenic seizure intensity (r = 0.991 and 0.962 for gamma-acetylenic and gamma-vinyl GABA respectively) and with degree of seizure protection (r = 0.974 and 0.834). Seizure intensity is reduced by 50% when brain GABA is increased to 265% and 264% of control values by the two inhibitors and seizure incidence is halved at 322% and 324%. Thus, audiogenic seizure protection in genetically susceptible mice is apparently a function of whole brain GABA concentrations.

4-Aminobutyrate Transaminase↗
PubMed1978

Blockade of epileptic responses in the photosensitive baboon, Papio papio, by two irreversible inhibitors of GABA-transaminase, gamma-acetylenic GABA (4-amino-hex-5-ynoic acid) and gamma-vinyl GABA (4-amino-hex-5-enoic acid).

The anticonvulsant potency and neurological toxicity of two new catalytic inhibitors of GABA-transaminase have been assessed in acute experiments in baboons with a natural syndrome of photic epilepsy. gamma-Acetylenic GABA, 160--200 mg/kg, or gamma-vinyl GABA, 450--950 mg/kg, intravenously, gave complete protection against generalised myoclonus or seizure responses induced by photic stimulation (in baboons without or with priming with subconvulsant doses of allylglycine). The protection became maximal 1--3 h after injection, and continued for 7--24 h. Signs characteristic of the acute toxicity of anticonvulsant drugs (nystagmus and ataxia) were not seen. The potential use of these compounds in human epilepsy deserves investigation.

4-Aminobutyrate Transaminase↗
PubMed1975

High affinity uptake of GABA in presumed GABA-ERGIC nerve endings in rat brain.

After interuption of the striato-nigral pathway uptake of gamma-aminobutyric acid (GABA) in the substatia nigra decresaed with 7 days to a constant level 30-40% of the normal. Concomitantly glutamate decarbosylase (GAD) was reduced to 10%. Hence about two-thirds of the GABA uptake activity in substantia nigra are localised, to the alleged GABA-ergic nerve elements originating from corpus striatum. The lesion resistant part of the uptake is probably not localised in cell bodies or large processes, since it was the same in tissuse prisms as in whole homogenates and crude nerve ending fractions. It was also not influenced by aminoozyacetic acid, which would argue against a localisation in glia. Whereas GAD was recovered mainly in a "heavy" nerve ending fraction, a large proportion of the GABA uptake was situated in a "light" fraction. After hemisections, GABA uptake was reduced to a similar extent in both fractions. It is suggested that whereas GAD is concentrated in nerve terminals, a significant proportion of the GABA uptake may be localised in preterminal axon branches in the substantia nigra. GABA uptake in the dorsal part of the lateral vestibular nucleus was not reduced by interruption of the Purkinje axons from the cerebellar vermis whereas GAD was reduced 50%. This indicates that the reuptake mechanism is not concentrated in the Prukinje axon terminals. In the hippocampus neither GABA nor GAD were reduced by lesions of afferent nerve pathoways, in accordance with previous results showing that in this region GABA producing neurones are intrinsic. The order of ratiols of GABA uptake to particulate GAD activity in different regions was: hippocampus greater than cerebellar cortex greater than substantia nigra greater than dorsal part of lateral vestibular necleus approximately equal to nucleus interpositus. The ratio may relfect the degree of specific localisation of the GABA uptake mechanism to the GABA-ergic structures.

Aminobutyrates↗
PubMed1979

Regulatory interrelations between GABA and polyamines. II. Effect of GABA on ornithine decarboxylase and putrescine levels in cell culture.

GABA added to rat hepatoma (HTC) cells in spinner culture at the time of induction of cell proliferation increased levels of ornithine decarboxylase (ODC) up to two- to threefold above that of control cells. The increases in ODC were also reflected by concomitant increases of intracellular putrescine levels, while spermidine and spermine were unchanged. GABA seems to have a direct stabilizing effect on ODC, since the turnover of the enzyme was slowed almost twofold when measured in cells treated with 10(-2) M GABA. The stabilizing effect is most pronounced for GABA, although some amino acids such as asparagine, glutamine, and lysine as well as some GABA analogues and homologues also tend to increase ODC but to a significantly lesser extent than GABA itself. GABA metabolites had no effect on ODC. S-Adenosylmethionine decarboxylase and tyrosine aminotransferase were not affected by the presence of GABA. The GABA effect on ODC may be important in certain types of cells for the regulation of polyamine biosynthesis.

Aminocaproates↗
PubMed1979

Amphetamine-induced circling behavior in rats: effects of unilateral microinjections of GABA and GABA-related drugs into substantia nigra.

In these experiments, the GABA control upon dopaminergic nigrostriatal neurons has been investigated using circling behavior in the rat. Chronically cannulated rats were given D-amphetamine (2 mg/kg i.p.) 45 min before unilateral microinjection (0.2 microliter/2 min) into the substantia nigra (SN) of GABA, muscimol, chlordiazepoxide (CDP) or bicuculline. Circling behavior was continuously recorded for 165 min using an automated rotometer. (1) Non-microinjected control rats exhibit a 'spontaneous' circling behavior after amphetamine. (2) When applied to the SN contralateral to the preferential side of the 'spontaneous' rotations, saline enhances contraversive circling; GABA (5 X 10(-5)M), CDP (5 X 10(-5)M) and muscimol (5 x 10(-7)M, 5 X 10(-8)M) counteract this effect and induce (except CDP) light ipsiversive rotations; GABA (10(-2)M) and muscimol (5 x 10(-5)M) further enhance contraversive turning. (3) When applied to the SN ipsilateral to the preferential side of the 'spontaneous' rotations, saline has no marked effect on the ipsiversive circling behavior but induces weak contraversive turning; GABA (5 X 10(-5)M), CDP (5 X 10(-5)M) and muscimol (5 x 10(-8)M) enhance the ipsiversive rotations; GABA (10(-2)M) and muscimol (5 x 10(-5)M) transiently decrease the ipsiversive circling; bicuculline (5 x 10(-5)M) induces a vigorous contraversive turning associated with a transient inhibition of the ipsiversive rotations. These results suggest that the activity of the nigral neurons is presumably stimulated by the microinjection itself, by bicuculline and, to a lesser extent, by high concentrations of GABA and muscimol, and inhibited by low concentrations of GABA, muscimol and CDP. These findings could further support the hypotheses of a GABAergic inhibitory control upon DA nigrostriatal pathways and of a GABA-like activity of CDP.

Animals↗
PubMed1979

Effects of GABA-analogues on the high-affinity uptake of GABA in astrocytes in primary cultures.

Employing primary cultures of astrocytes which seem to constitute a valid model of their in vivo counterparts, it has been demonstrated that this cell type is likely to be of importance in terminating the transmitter activity of GABA. It has been shown that the transport carrier in astrocytes is stereospecific for the C-4 hydrogens of the GABA molecule and that its structural requirements are distinct from those exhibited by the neuronal GABA carrier. beta-Proline was a selective inhibitor of GABA transport in astrocytes, whereas R-trans-4-methyl-4-aminocrotonic acid and S-nipecotic acid seemed to be selective inhibitors of neuronal GABA transport, as studied using very thin slices ("prisms") of brain cortex. These findings may be important for studies on the relative significance of the two transport systems in GABA-mediated neurotransmission, and thus for future pharmacological manipulations of the GABA system. This may eventually be beneficial for the treatment of neurological disorders such as epilepsy, Huntington's chorea and Parkinson's disease in which the GABA system seems to be disturbed (34,60,62).

4-Aminobutyrate Transaminase↗
PubMed1978

The effect of gamma-acetylenic GABA, an enzyme-activated irreversible inhibitor of GABA-transaminase, on dopamine pathways of the extrapyramidal and limbic systems.

gamma-Acetylenic GABA (100 mg/kg i.p.) inhibited GABA-transaminase activity and caused a several-fold increase in the concentration of GABA in rat brain. This increased GABA concentration was associated with a decreased rate of dopamine depletion following alpha-methyl-p-tyrosine treatment and a decrease in homovanillic acid in extrapyramidal and limbic structures suggesting a decrease in dopamine turnover in both pathways. In addition, gamma-acetylenic GABA injected into the ventral mesencephalic tegmentum decreased dopamine turnover in the mesolimbic forebrain. These results are consistent with a modulatory function of GABAergic neurons on extrapyramidal and limbic dopamine pathways. Inhibitory effects on dopaminergic functions of the extrapyramidal and limbic systems were also indicated by the amphetamine and apomorphine-induced ipsilateral turning after unilateral substantia nigral injections of gamma-acetylenic GABA and by the attenuation of dopamine-induced hypermotility after bilateral injections of gamma-acetylenic GABA into the nucleus accumbens.

4-Aminobutyrate Transaminase↗
PubMed1979

Hypersynchronisation and sedation produced by GABA-transaminase inhibitors and picrotoxin: does GABA participate in sleep control?

Systemic administration of GABA-transaminase inhibitors, gamma-acetylenic GABA (100 mg/kg) or gamma-vanylic GABA (1200 mg/kg) produces behavioral picture of somnolence accompanied by EEG hypersynchronisation reminiscent of electrographic signs of petit mal epilepsy. Similarly, systemic administration of GABA antagonist, Picrotoxin (3--4 mg/kg) produces a short lasting period of sedation preceding the development of myoclonic jerks which is also accompanied by Wave-spike discharges. The role of GABA in sleep control is discussed. Although the area is not ready for firm conclusions, the results suggest that hyperactivity of GABA-ergic system as well as its hypoactivity could mediate pathological somnolence associated with different forms of epilepsy.

4-Aminobutyrate Transaminase↗
PubMed1979

Distribution of gaba-receptors and gaba-carriers in the mammalian nervous system.

1. Extrasynaptic GABA-receptors occur on both neurone somata and unmyelinated axons in the mammalian peripheral nervous system. Activation of these receptors leads to depolarization, reduced spike amplitude and slowed conduction, probably mediated through increased Cl- conductance. 2. GABA also depolarizeds preganglionic nerve terminals in the rat superior cervical ganglion and reduces the release of acetylcholine by preganglionic nerve impulses. 3. The Schwann and satellite neuroglial cells surrounding peripheral unmyelinated axons and neurones possess a GABA-carrier promoting net uptake of GABA at external concentrations greater than or equal to 1 microM. 4. The possible significance of extrasynaptic receptors and carriers for GABA is discussed.

Animals↗
PubMed1979

Stoichiometry of GABA-receptor interactions: GABA modulates the glycine-receptor interaction allosterically in a vertebrate neuron.

1. Measurement of steady-state conductance changes provides a reliable method for determination of transmitter-receptor stoichiometry in general and for GABA and its receptor interactions in particular. Log-log plotting of steady-state conductance changes as a function of decreasing transmitter concentration gives the molecularity of the interaction as a limiting slope. 2. Suitable measurements of GABA action in locust muscle show a molecularity of 3 with strong positive cooperativity. One molecule of picrotoxin is sufficient to block this reaction. Kinetic studies reveal the presence of occult desensitization. Thermodynamic studies reveal strong negative heats of interaction compatible with conformational changes in a multi-subunit receptor. 3. Measurements in the lateral dendrite of the goldfish Mauthner cell reveal that glycine has a more powerful action than GABA. Both interactions, however, utilize 4 molecules of amino acid with strong positive cooperativity to activate its receptors. The receptors are apparently distinct and there appears to be a higher glycine-receptor density. 4. In addition to its action on its own receptor, GABA allosterically modulates the glycine-receptor interaction in the Mauthner cell by lowering the energy barrier for the binding of the first glycine molecule, thereby increasing the affinity of glycine for its receptor.

Allosteric Regulation↗
PubMed1978

Effects of some conformationally restricted GABA analogues on GABA membrane binding and nerve ending transport.

By using a series of aminocyclopentane- and aminocyclohexanecarboxylic acids, as well as some naturally occurring amino acids, it was possible to determine some aspects of the spatial topography of the GABA membrane binding and transport sites. The NA-independent GABA binding site was found to have a different spatial topography than the Na-dependent binding site in that trans-3-aminocyclopentanecarboxylic acid (trans-3-ACPC) was 7 times more potent than cis-3-ACPC to inhibit Na-independent binding, but only 1.6 times more potent to inhibit Na-dependent binding. The nerve ending GABA transport site was found to be similar to the Na-dependent GABA binding site in that it will accommodate both cis- and trans-3-ACPC. However, the transport site differs from the binding site in that cis-3-aminocyclohexanecarboxylic acid (cis-3-ACHC) is a potent inhibitor of transport but a weak inhibitor of binding. In addition to the differences in spatial characteristics, differences in the subcellular distribution of Na-independent and Na-dependent binding sites were observed. The former were found primarily in the nerve ending-mitochondrial fraction, while the latter were primarily found in the microsomal fraction.

Aminobutyrates↗
PubMed1977

Rotational behavior induced in rats by intranigral application of GABA-related drugs and GABA antagonists.

GABA and GABA-related drugs such as muscimol, gamma-hydroxybutyric acid and baclofen injected unilaterally into the substantia nigra of rats elicited contraversive turning. Unilateral injections of picrotoxin and bicuculline produced either ipsi- or contraversive turning depending on the volume of vehicle. I.p. applied haloperidol did not abolish the muscimol-induced turning. This and the direction of rotational behavior suggests that the turning behavior elicited by GABA-related drugs is not mediated by the nigrostriatal dopaminergic tract.

Aminobutyrates↗
PubMed1979

Regulatory interrelations between GABA and polyamines. I. Brain GABA levels and polyamine metabolism.

Elevation of brain GABA levels by GABA-T inhibition is accompanied by a decrease of S-adenosylmethionine decarboxylase activity. This is followed by an increase of ornithine decarboxylase activity and a severalfold increase of brain putrescine levels. Spermidine and spermine levels are not significantly affected under these conditions. These unexpected findings support a regulatory interaction between GABA and polyamine metabolism.

4-Aminobutyrate Transaminase↗