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At least 1,153 records · Page 64Linked to original sources
PubMed1988

Electrophysiological actions of norepinephrine in rat lateral hypothalamus. II. An in vitro study of the effects of iontophoretically applied norepinephrine on LH neuronal responses to gamma-aminobutyric acid (GABA).

The preceding studies demonstrated that norepinephrine (NE) can consistently augment synaptically mediated (70%) and gamma-aminobutyric acid (GABA)-induced (69%) inhibitory responses of lateral hypothalamic (LH) neurons in vivo. The present experiments further characterized the interactions of NE with LH neuronal responses to GABA in terms of alpha- and beta-receptor mechanisms and demonstrated the utility of the in vitro LH tissue slice preparation as a model for future extra- and intracellular studies of NE modulatory phenomena. Extracellular activity of LH cells was recorded from diencephalic slices (450 microns) incubated in artificial cerebrospinal fluid at 33 degrees C. Interactions between iontophoretically applied NE, isoproterenol (ISO) or phenylephrine (PE) and responses of LH neurons (n = 64) to GABA microiontophoresis were quantitated and characterized using computer-generated ratemeter and histogram records. This analysis revealed two distinct actions of NE on GABA-induced responses of LH neurons. In 8 of 32 cells tested (25%), locally applied NE markedly enhanced inhibitory responses to GABA iontophoresis in a manner identical to that observed in vivo. However, in 20 cells (62.5%), iontophoretic application of NE produced a clear antagonism of GABA responses. NE also exerted dual effects on the background firing rate of LH neurons, causing both inhibition and excitation. Overall, in those cells where NE administration increased spontaneous discharge, it either antagonized or had no effect on GABA-mediated inhibition. In contrast, spontaneous firing rate was never elevated above control levels in those cases where NE potentiated GABA responses. Additional experiments demonstrated that the GABA potentiating actions of the benzodiazepine, flurazepam, were preserved in LH tissue slice preparations. In addition, iontophoretic application of the beta-agonist, ISO, routinely suppressed the spontaneous activity of LH neurons and mimicked the facilitating action of NE on GABA. Likewise, microiontophoretic application of 8-bromo cyclic adenosine monophosphate (AMP) enhanced GABA-induced inhibition of LH firing rate in each of 11 cells tested. On the other hand, local administration of the alpha agonist, PE, routinely produced NE-like antagonism of GABA inhibition along with increases in spontaneous firing rate. Taken together these findings indicate that the commonly observed in vivo phenomena of NE augmentation of GABA and suppression of LH neuron spontaneous firing can be demonstrated in vitro, and most likely result from activation of beta adrenoceptors and subsequent elevation of cyclic AMP levels.(ABSTRACT TRUNCATED AT 400 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1990

Role of gamma-aminobutyric acid in the zona incerta in the control of luteinizing hormone release and ovulation.

gamma-Aminobutyric acid (GABA) neurones are present in the zona incerta (ZI) where other systems have been shown to influence gonadotrophin release. This report investigates the effect of GABA agents in the ZI on ovulation and luteinizing hormone (LH) release. In intact females under Saffan anaesthesia, bilateral stereotactic injections into the ZI of two GABA transaminase inhibitors [amino(oxy)acetic acid and gamma-acetylene GABA] on the morning of pro-estrus or two GABA agonists on the afternoon of pro-estrus inhibited ovulation. The selective GABA B agonist baclofen was effective at 0.05 nM; muscimol, a mixed GABA A and B agonist, was 50-fold less potent, while the selective GABA A agonist isoguvacine had no effect at 500 nM. Administration of baclofen at 0.05 and 5 nM into the ZI significantly reduced plasma LH concentration in untreated ovariectomized rats and also prevented the rise in LH normally induced in ovariectomised rats primed with 5 micrograms oestradiol benzoate (OB) plus 0.5 mg progesterone. In ovariectomised rats primed with 5 micrograms OB alone, administration of the selective GABA A antagonist bicuculline (200 and 260 pg/side) had no effect on plasma LH, while the GABA B antagonist phaclofen (10 pg/side) stimulated a rise in plasma LH, 40 and 60 min after injection. These results indicate that GABA activity in the ZI exerts an inhibitory effect on LH release and ovulation and this is preferentially exerted via GABA B receptors.

4-Aminobutyrate Transaminase↗
PubMed2004

Postsynaptic localization of gamma-aminobutyric acid transporters and receptors in the outer plexiform layer of the goldfish retina: An ultrastructural study.

The gamma-aminobutyric acid (GABA)-ergic system in the outer plexiform layer (OPL) of the goldfish retina was studied via light and electron immunohistochemistry. The subcellular distributions of immunoreactivity (-IR) of plasma membrane GABA transporters GAT2 and GAT3, the alpha1 and alpha3 subunits of the ionotropic GABA(A) receptor, and the rho1 subunit of the ionotropic GABA(C) receptor were determined. The localization of the GAT2-IR and GAT3-IR to horizontal cell dendrites at the base of the cone synaptic complex was the main characteristic at the ultrastructural level. Very rarely, GAT2-IR and GAT3-IR were found in horizontal cell dendrites innervating rod spherules. alpha1-IR and alpha3-IR were seen in wide bands in the OPL, whereas rho1-IR appeared as a narrow band in the OPL. Most alpha1-IR was intracellular in rod and cone terminals. Membrane-associated alpha1-IR was observed in cone pedicles but not in rod spherules; postsynaptic elements were also labeled. alpha3-IR was concentrated in the lateral elements of horizontal cell dendrites in cone pedicles. In contrast, rho1-IR was found mainly on the spinules of the horizontal cell dendrites in cone pedicles. In addition, in another type of cone pedicle, rho1-IR was found at the position of OFF-bipolar cell dendrites. alpha3-IR and rho1-IR were rarely found in horizontal cell dendrites innervating rods. We suggest that two GABAergic pathways exist in the outer retina- first, a GABAergic positive loop with GABA receptors mainly on the horizontal cell dendrites and spinules and, second, a GABAergic feedback pathway involving GABA receptors on cone pedicles and GABA transporters on horizontal cells and that this pathway presumably modulates feedback strength from horizontal cells to cones.

Animals↗
PubMed1991

Gamma-aminobutyric acid controls the mouse hypothalamic-pituitary-testicular response to the presence of female.

The role of gamma-aminobutyric acid (GABA) in the control of plasma testosterone was studied on male mice of inbred strains (CBA/Lac, A/He and BALB/c) exposed to a sexually receptive female in the same cage but separated by a partition. Within 40 minutes, testosterone levels in plasma increased 1.5-3.5 times depending upon the mouse genotype. This process could be completely blocked if GABA accumulation was induced by pretreatment with the GABA transaminase inhibitor, aminooxyacetic acid (AOAA), or by emotional stress induced by 40 min of restraint. Neither bicuculline-induced blockade of GABA receptors nor a decrease of GABA concentration induced by prior administration of thiosemicarbazide (an inhibitor of glutamate decarboxylase), affected the increase of plasma testosterone that occurred in response to presentation of a receptive female. However, at sexual arousal, the bicuculline blockade of GABA receptors significantly reduced the inhibitory effects of both AOAA administration and emotional stress on plasma testosterone levels. We conclude that the inhibitory effect of emotional stress on female-induced activation of testicular endocrine function is mediated, at least in part, via activation of bicuculline-sensitive receptors.

Aminooxyacetic Acid↗
PubMed1989

[The effect of ethanol on gamma-aminobutyric acid in the brain].

The effect of acute and chronic ethanol administration on the level of gamma-aminobutyric acid (GABA), glutamate, aspartate, and glutamine was investigated. The level of GABA rose both after acute and chronic ethanol administration. In chronic experiments also the level of glutamate, aspartate and glutamine were increased. In acute experiments the incorporation from glucose into the studied amino acids (neuronal compartment) increased, while in chronic experiments a decreasing trend was observed. In the glial compartment the incorporation increased only into glutamate and glutamine in acute experiments, while in chronic experiments a decreased incorporation into glutamine was recorded. The activities of three enzymes were studied in seven parts of the brain after acute ethanol administration. The activity of glutamic acid decarboxylase increased in the hypothalamus and brain cortex and decreased in the medulla oblongata. The activity of GABA transaminase did not change and the activity of glutamine synthetase decreased only in the hippocampus. In accordance with several other studies, the presented results show that ethanol interferes with the GABA system in the brain. It is suggested that the primary effect of ethanol is exerted on the cell membranes with preference for the regions connected with the GABA system.

4-Aminobutyrate Transaminase↗
PubMed1985

Uptake of gamma-aminobutyric acid by human blood platelets: comparison with CNS uptake.

Human blood platelets show a sodium and temperature dependent uptake of gamma-aminobutyric acid (GABA) and other neuroactive amino acids. The most potent inhibitors tested of platelet GABA uptake were taurine and beta-alanine, while nipecotic acid and cis-3-aminocyclohexanecarboxylic acid were relatively weak inhibitors. These results suggest GABA is transported by a beta-amino acid uptake process in human platelets. Thus, platelet GABA uptake may more closely resemble glial rather than neuronal uptake.

Amino Acids↗
PubMed1981

Differential solubilization of gamma-aminobutyric acid receptive sites from membranes of mammalian brain.

Sodium-dependent (+Na) and sodium-independent (-Na) receptive sites for gamma-aminobutyric acid (GABA) residing in or on frozen synaptic plasma membranes (SPM) of bovine cerebral cortex were characterized as to binding constants, pharmacologic specificities, and sodium dependence. The SPM fraction was then treated with various concentrations of Triton X-100 resulting in the loss of pharmacologic specificity, binding characteristics, and sodium dependence associated with +Na GABA receptive sites in SPM. The resulting junctional complex preparation (JC), i.e., a fraction enriched in junctional complexes, possessed only the pharmacologic specificity and binding constants associated with -Na receptive sites whether assayed in the presence or absence of 100 mM-NaCl. This is probably due to the detergent dispersal or solubilization of the +Na GABA receptive site. The binding constants, KD and Bmax, for -Na GABA binding in SPM were 170 nM and 4.4 pmol/mg protein, while in JC they were 186 nM and 3.7 pmol/mg protein. Under repeated washing the KD was reduced to 60 +/- 6.9 nM and the Bmax was reduced to 2.5 +/- 0.5 pmol/mg protein in JC, probably owing to the removal of endogenous ligand or inhibitor, and not to inhibition by residual Triton X-100. Multiple extraction with 0.1% or 0.5% Triton X-100 did not alter the KD or Bmax values for the binding of [3H]GABA to JC. Sodium-independent GABA binding was lost from JC membranes with the use of sodium deoxycholate, probably through solubilization.

Animals↗
PubMed1987

An electrophoretic method for the determination of the proportion of gamma-aminobutyric acid in a mixture of labeled neurotransmitter and its catabolites.

An electrophoretic method for the separation of gamma-aminobutyric acid (GABA) from its metabolites after GABA-transaminase attack is presented. The method is based on the fact that at neutral pH GABA has no net electrical charge, whereas its major metabolites, succinic acid and Krebs cycle intermediates, are negatively charged. The method appears to be especially suitable for evaluation of true-labeled neurotransmitter within the radioactivity which is found in synaptosomes after labeled GABA-uptake studies.

4-Aminobutyrate Transaminase↗
PubMed1996

The uptake of gamma-aminobutyric acid and glutamate by synaptosomes from the visual cortex of albino and pigmented rabbits.

The synaptosomal uptake of glutamate and gamma aminobutyric acid [GABA] in the visual cortex of albino and pigmented rabbits was compared. GABA uptake was similar in both pigmented and albino rabbits, but glutamate uptake was greater in the pigmented rabbit. The kinetics of glutamate uptake in albino and pigmented rabbits suggested that the number of functioning glutamate synapses may be lower in the albino. The significance of this with respect to the differences in visual processing in the two types of rabbit is discussed.

Albinism↗
PubMed1997

The membrane topology of GAT-1, a (Na+ + Cl-)-coupled gamma-aminobutyric acid transporter from rat brain.

The membrane topology of GAT-1, a sodium- and chloride-coupled gamma-aminobutyric acid transporter from rat brain, has been probed using N-glycosylation scanning mutagenesis. Overall, the results support the theoretical 12-transmembrane segment model. This model (based on hydropathy analysis) was originally proposed for GAT-1 and adopted for all other members of the sodium- and chloride-dependent neurotransmitter transporter superfamily. However, our data indicate that the loop connecting putative transmembrane domains 2 and 3, which was predicted to be located intracellularly, can be glycosylated in vivo. Furthermore, studies with permeant and impermeant methanesulfonate reagents suggest that cysteine 74, located in the hydrophilic loop connecting transmembrane domains 1 and 2, is intracellular rather than extracellular. We present a model in which the topology deviates from the theoretical one in the amino-terminal third of the transporter. It also contains 12 transmembrane segments, but the highly conserved domain 1 does not form a conventional transmembrane alpha-helix.

Amino Acid Sequence↗
PubMed1982

Excitability of primary afferents in feline spinal cord: taurine, homotaurine, and gamma-aminobutyric acid compared.

Effects of taurine and homotaurine (3-aminopropanesulfonic acid), on excitability of primary afferents were compared with effects of gamma-aminobutyric acid (GABA) in spinal unanaesthesized cats. Homotaurine and GABA, administered intravenously or topically, produced a marked increase in afferent excitability. Homotaurine was about 10 times more potent than GABA. Taurine (up to 2 mmol/kg i.v., or 10 mM topically) did not produce a consistent change in afferent excitability. The effect of homotaurine was antagonized by bicuculline or picrotoxin in doses which suppressed the primary afferent depolarization, as indicated by an increase of afferent excitability, evoked by conditioning stimulation of an antagonistic muscle nerve. Semicarbazide, an inhibitor of GABA synthesis, did not attenuate the homotaurine-induced excitability changes of afferents while suppressing entirely the primary afferent depolarization. These findings suggest that homotaurine exerts a direct GABA-like action on feline primary afferents.

Afferent Pathways↗
PubMed1980

gamma-Aminobutyric acid stimulates intrinsic inhibitory and excitatory nerves in the guinea-pig intestine.

The sites of action of gamma-aminobutyric acid (GABA) were examined in preparations of the distal colon and ileum of guinea pigs. GABA caused transient relaxations of the longitudinal and circular muscle of the colon and transient contractions followed by relaxation of the muscle of the ileum. The responses of both parts of the intestine were antagonized by tetrodotoxin and by bicuculline. Nerve-free preparations of the longitudinal muscle of the ileum were not affected by GABA, even in concentrations up to 10(-4) g/ml. There was a marked tachyphylaxis of the responses to GABA. Relaxations in response to GABA were not affected by pentolinium or by a combination of phentolamine and propranolol. Contractions in response to GABA were blocked by hyoscine. Neither the ascending excitatory or descending inhibitory components of the peristaltic reflex in the distal colon were affected by bicuculline or by making the intestine tachyphylactic to GABA. The results indicate that GABA stimulates receptors mediating excitation of cholinergic excitatory and enteric inhibitory neurons whereas it has little or no direct effect on the muscle of the ileum or distal colon.

Amino Acids↗
PubMed1986

Elevated gamma-aminobutyric acid level in striatal but not extrastriatal brain regions in Parkinson's disease: correlation with striatal dopamine loss.

We measured the concentration of gamma-aminobutyric acid (GABA), glutamic acid, and o-phosphoethanolamine in autopsied brain of 9 patients who died with idiopathic Parkinson's disease and 10 control subjects. In the control striatum GABA showed an uneven rostrocaudal distribution pattern with rostral subdivisions containing about 40 to 50% higher levels. When compared with controls, GABA concentrations in Parkinson's disease striatum were generally elevated. The GABA elevation was most pronounced in the caudal subdivision of the putamen; this striatal subdivision also showed the most severe dopamine loss. We observed in the caudal putamen a significant negative correlation between the (elevated) GABA and (reduced) dopamine levels (the latter expressed as the sum of dopamine plus 3-methoxytyramine). Milder nonsignificant elevations of GABA levels were observed in intermediate and rostral putamen followed by the caudate head subdivisions. GABA levels were normal in all extrastriatal brain areas examined. Striatal glutamic acid levels were markedly elevated in 3 of the 9 patients with Parkinson's disease. We suggest that the altered GABA metabolism in the striatum, especially the putamen, is consequent to the nigrostriatal deficiency in this disorder. This secondary change in striatal GABA function is likely to contribute to the basal ganglia dysfunction produced by the striatal dopamine loss and thus may be related to certain aspects of parkinsonian symptomatology.

Brain Chemistry↗
PubMed2005

Expression of rice glutamate decarboxylase in Bifidobacterium longum enhances gamma-aminobutyric acid production.

Bifidobacteria are important for the production of fermented dairy products and probiotic formulas but have a low capacity for gamma-aminobutyric acid (GABA) production. To develop a Bifidobacterium strain with an enhanced GABA production, we transformed Bifidobacterium longum with a rice glutamate decarboxylase (OsGADC(-)) gene by electroporation. When the transformed strain was cultured in medium containing monosodium glutamate, the amount of GABA increased significantly compared with those of untransformed Bifidobacterium. Thus, by introducing a plant derived GAD gene, a Bifidobacterium strain has been genetically engineered to produce high levels of GABA from glutamate.

Bifidobacterium↗
PubMed1985

Phospholipid-induced changes of gamma-aminobutyric acid transport in cortex grey matter in culture.

The function of membrane phospholipids (PL) in the regulation of gamma-aminobutyric acid (GABA) transport and GABA carrier binding has been investigated in organized cultures of rat cerebral cortex. The cellular lipid composition has been changed by growing the cells in a delipidated nutrient solution or by short-term exposure of the cells to PL emulsions. Introduction of PL into the cellular matrix was monitored by analysis of biologically active fluorescently labeled phosphatidylcholine (PC) or phosphatidylethanolamine (PE). Parinaroyl and dansyl derivatives were used. Conditions of maintenance as well as exogenously given PL affected the transport of GABA. Two transport systems were observed, one first-order system and one cooperative system. Saturated species of PC or PE reduced first-order GABA uptake with increase in chain length of the fatty acid residues. The effects of unsaturated PL were dependent upon the polar head. Unsaturated PC enhanced the capacity of the first-order transport of the amino acid. In comparison to cultures grown in lipid-free medium, introduction of diarachinoyl-PC into the cells increased the density of the first-order active transport sites by a factor of 8 and the affinity constant by a factor of 17. Diarachinoyl-PE reduced both kinetic parameters. GABA uptake via the cooperative system was enhanced by the unsaturated PE, not by PC. The role of endogenous PL and their asymmetric distribution was studied by application of phospholipase A2, C, and D. Stimulation of carrier activity was induced by hydrolysis of PL on the external leaflet. Inhibition occurred upon enzymatic degradation of external and cytoplasmic PL. Lipolysis also affected GABA receptor binding, suggesting that the effects observed represent the activity of both classes of binding sites, the carrier and the receptor. However the latter accounted for a small fraction of the binding. Transport of the amino acid was temperature sensitive. The temperature curve was shifted within two discontinuities, appearing in the Arrhenius plot as a function of membrane lipids. The results suggest a partitioning of the proteins between fluid and ordered lipid domains. Displacement of the protein may govern the rate constants and/or the effective protein concentration.

Animals↗
PubMed2005

Resuscitative effect of a gamma-aminobutyric acid B receptor antagonist on gamma-hydroxybutyric acid mortality in mice.

STUDY OBJECTIVE: In the present study, a number of compounds were tested to evaluate their efficacy in exerting a protective effect on gamma-hydroxybutyric acid (GHB)-induced mortality in mice. The drugs investigated were the gamma-aminobutyric acid B (GABA B ) receptor antagonist SCH 50911, the GABA A receptor antagonist bicuculline, the benzodiazepine receptor antagonist flumazenil, the putative GHB receptor antagonist NCS-382, the opioid receptor antagonist naltrexone, and the amino acid and possible neuromodulator, taurine. METHODS: All mice were initially treated with a lethal dose of GHB (7 g/kg, administered intragastrically). Once mice had displayed clear signs of GHB intoxication, animals from each group were treated acutely with either SCH 50911 (vehicle; 75, 150, and 300 mg/kg, administered intraperitoneally), bicuculline (vehicle; 2, 4, 6, and 8 mg/kg, administered intraperitoneally), flumazenil (vehicle; 1, 3, and 10 mg/kg, administered intraperitoneally), NCS-382 (vehicle; 50 and 200 mg/kg, administered intraperitoneally), naltrexone (vehicle; 3 and 10 mg/kg, administered intraperitoneally), or taurine (vehicle; 250 and 750 mg/kg, administered intraperitoneally). The various doses of each single drug were administered to 10 mice, randomly allocated throughout the experimental groups. Mortality was recorded every hour for the first 9 hours and subsequently 12, 18, and 24 hours after GHB injection. RESULTS: In each experiment, all vehicle-treated mice died within 24 hours of GHB injection. Doses of 150 and 300 mg/kg SCH 50911 produced a marked protection on GHB-induced mortality, evidenced by the death of only 0 of 10 and 2 of 10 mice in the 150- and 300-mg/kg SCH 50911 groups, respectively. In contrast, at all doses tested, bicuculline, flumazenil, NCS-382, naltrexone, and taurine were not observed to exert any protective effect on GHB-induced mortality (9 to 10/10 mice died in each treatment group). CONCLUSION: These results suggest an involvement of the GABA B receptor, at least in rodents, in the mediation of the lethal effects of GHB.

Animals↗