Effects Of Γ-aminobutyric Acid Research Articles

EFFECT OF GAMMA-AMINOBUTYRIC ACID UPON BRUCINE CONVULSIONS.

EFFECT OF GAMMA-AMINOBUTYRIC ACID UPON BRUCINE CONVULSIONS.

Central hypotensive effect of γ-aminobutyric acid in anaesthetized dogs

Central hypotensive effect of γ-aminobutyric acid in anaesthetized dogs

Effect of γ-amino Butyric Acid on Limpet Populations: Towards the Future Management and Conservation of Endangered Patellid Species

Many neurotransmitters, such as γ-amino butyric acid (GABA), can act as chemical cues influencing settlement and metamorphosis in benthic marine invertebrates. This effect has been described especially in mollusks, such as mussels, clams, or haliotids. This study describes the first record of the effect of GABA on patellogastropod populations. Special attention was paid to the effect of the compound on recruitment processes. The experiment was carried out using 10 × 10cm artificial limestone plates that were drilled into intertidal rocks at different inclinations, and periodically treated with a 1mM GABA solution. A total of five limpet species was considered (four patellid limpet species and the pulmonate Siphonaria pectinata). Each individual recorded on the plates as well as within a 20 × 20cm quadrant was measured, identified to species level, and its straight-line distance to the application point was registered. Treated surfaces were the first to possess both adults and recruits. Individuals also were found in a higher number around GABA-treated plates than around controls. The results indicated that the compound may not only enhance recruitment, but also might accelerate it. Recruits were located at higher distances from GABA treated plates than from control surfaces. This supports the hypothesis that this is the life history stage most sensitive to the compound. The behavior shown by the individuals belonging to the two endangered patellid species present in the study area (Patella ferruginea and Cymbula nigra) also were analyzed. For the former, the results indicated that the use of GABA may have similar effects on recruitment similar to the presence of adult conspecifics. This is the first report of the effect of GABA on patellid limpet recruitment and population dynamics. Conservational implications of the results are discussed.

Functional evidence for different roles of GABAA and GABAB receptors in modulating mouse gastric tone

The aims of the present study were to investigate, using mouse whole stomach in vitro, the effects of gamma-aminobutyric acid (GABA) and GABA receptor agonists on the spontaneous gastric tone, to examine the subtypes of GABA receptors involved in the responses and to determine the possible site(s) of action. GABA induced gastric relaxation, which was antagonized by the GABA(A)-receptor antagonist, bicuculline, potentiated by phaclofen, GABA(B)-receptor antagonist, but not affected by 1,2,5,6-Tetrahydropyridin-4-yl methylphosphinic acid hydrate (TPMPA), GABA(C)-receptor antagonist. Muscimol, GABA(A)-receptor agonist, mimicked GABA effects inducing relaxation, which was significantly reduced by bicuculline, N omega-nitro-L-arginine methyl ester (L-NAME), inhibitor of NO synthase or apamin, inhibitor of small conductance Ca(2+)-dependent K(+) channels, which blocks the purinergic transmission in this preparation. It was abolished by tetrodotoxin (TTX) or l-NAME plus apamin. Baclofen, a specific GABA(B)-receptor agonist, induced an increase in the gastric tone, which was antagonized by phaclofen and abolished by TTX or atropine. Bicuculline, but not phaclofen or TPMPA, per se induced an increase in gastric tone, which was prevented by L-NAME. In conclusion, our results suggest that GABA is involved in the regulation of mouse gastric tone, through modulation of intrinsic neurons. Activation of GABA(A)-receptors mediates relaxation through neural release of NO and neurotransmitters, activating Ca(2+)-dependent K(+) channels, likely purines, while activation of GABA(B)-receptors leads to contraction through acetylcholine release.

Effects of γ-aminobutyric acid (GABA) agonists and a GABA uptake inhibitor on pharmacoresistant seizure like events in organotypic hippocampal slice cultures

Seizure like events (SLEs) induced by low magnesium or 4-aminopyridine in organotypic hippocampal slice cultures (OHSCs) are resistant to standard antiepileptic drugs including phenobarbital, and 1,4-benzodiazepines [Albus, K., Wahab, A., Heinemann, U., 2008. Standard antiepileptic drugs fail to block epileptiform activity in rat organotypic hippocampal slice cultures. Br. J. Pharmacol. 154, 709-724]. The present study was undertaken in order to test the effects of other compounds on SLEs in OHSCs that enhance GABA-mediated actions. Six to 12 days old Wistar rats were used to cultivate OHSCs according to the interface method [Stoppini, L., Buchs, P.A., Muller, D., 1991. A simple method for organotypic cultures of nervous tissue. J. Neurosci. Methods 37, 173-182]. Neuronal activity and extracellular potassium concentration were recorded under submerged conditions. SLEs were induced by lowering the magnesium concentration. The effects of GABA(A) agonists muscimol and isoguvacine, the GABA(B) agonist baclofen, the GABA uptake blocker nipecotic acid and the neurosteroid alfaxalone on induction and ongoing SLEs were analyzed. Low magnesium induced SLEs were dose dependently suppressed by the GABA(A) receptor agonists muscimol, isoguvacine and alfaxalone and by the GABA uptake inhibitor nipecotic acid whereas the GABA(B) receptor agonist baclofen attenuated but did not suppress SLE. Our findings demonstrate that in OHSCs GABA has an inhibitory effect on SLEs. Proconvulsant effects of GABA agonists on spontaneous neuronal activity and seizure like activity were never observed. Our findings exclude a possible contribution of impaired/altered GABA-ergic mechanisms based on immaturity of receptors and/or low receptor density to seizure susceptibility and pharmacoresistance in OHSCs.

W1916 Proliferative Effects of γ-Aminobutyric Acid On the Gastric Cancer Cell Line Are Associated with Extracellullar Signal-Regulated Kinase 1/2 Activation

W1916 Proliferative Effects of γ-Aminobutyric Acid On the Gastric Cancer Cell Line Are Associated with Extracellullar Signal-Regulated Kinase 1/2 Activation

The Effects of γ-Aminobutyric Acid, Vinegar, and Dried Bonito on Blood Pressure in Normotensive and Mildly or Moderately Hypertensive Volunteers

The purpose of this study was to examine the effects of γ-aminobutyric acid (GABA) in fermented drinking water prepared from sodium glutamate, vinegar, and dried bonito (FDWG) compared with placebo [vinegar and dried bonito without GABA (FDW)] and its safety in normotensive and mildly or moderately hypertensive volunteers. A double-blind, placebo-controlled, randomized study was conducted involving volunteers with normal (group-N) and mildly or moderately high (group-H) blood pressure (BP). After a pretreatment period of 2 weeks (weeks –2), the subjects received FDWG or FDW for 12 weeks followed by 4 weeks of no intake (weeks 16). In group-H, both FDWG and FDW significantly decreased systolic (SBP, −7.6 ± 4.0 and −5.5 ± 1.5 mmHg, p<0.05, respectively) and diastolic (DBP, −10.6 ± 4.0 and −7.6 ± 1.7 mmHg, p<0.01, respectively) BP compared to the baseline (0-week) value at 12 weeks, respectively. There were no abnormal changes in hematological or blood chemistry variables, urinalysis, heart rate, or body weight in the study groups. These findings indicated that vinegar and dried bonito with or without GABA might have an effect on BP in mildly or moderately hypertensive patients.

Functional evidence for GABA as modulator of the contractility of the longitudinal muscle in mouse duodenum: Role of GABA A and GABA C receptors

We investigated, in vitro, the effects of γ-aminobutyric acid (GABA) on the spontaneous mechanical activity of the longitudinal smooth muscle in mouse duodenum. GABA induced an excitatory effect, consisting in an increase in the basal tone, which was antagonized by the GABA A-receptor antagonist, bicuculline, potentiated by (1,2,5,6-Tetrahydropyridin-4-yl)methylphosphinic acid hydrate (TPMPA), a GABA C-receptor antagonist and it was not affected by phaclofen, a GABA B-receptor antagonist. Muscimol, GABA A receptor agonist, induced a contractile effect markedly reduced by bicuculline, tetrodotoxin (TTX), hexamethonium and atropine. Cis-4-aminocrotonic acid (CACA), a specific GABA C receptor agonist, induced an inhibitory effect, consisting in the reduction of the amplitude of the spontaneous contractions and muscular relaxation, which was antagonised by TPMPA, GABA C-receptor antagonist, TTX or N ω-nitro- l-arginine methyl ester (L-NAME), nitric oxide (NO) synthase inhibitor, but not affected by hexamethonium. In conclusion, our study indicates that GABA is a modulator of mechanical activity of longitudinal muscle in mouse duodenum. GABA may act through neuronal presynaptic receptors, namely GABA A receptors, leading to the release of ACh from excitatory cholinergic neurons, and GABA C receptors increasing the release of NO from non-adrenergic, non-cholinergic inhibitory neurons.

Activation of γ‐aminobutyric acid GAT‐1 transporters on glutamatergic terminals of mouse spinal cord mediates glutamate release through anion channels and by transporter reversal

The effects of gamma-aminobutyric acid (GABA) on the release of glutamate from mouse spinal cord nerve endings have been studied using superfused synaptosomes. GABA elicited a concentration-dependent release of [3H]D-aspartate ([3H]D-ASP; EC50= 3.76 microM). Neither muscimol nor (-)baclofen mimicked GABA, excluding receptor involvement. The GABA-evoked release was strictly Na+ dependent and was prevented by the GABA transporter inhibitor SKF89976A, suggesting involvement of GAT-1 transporters located on glutamatergic nerve terminals. GABA also potentiated the spontaneous release of endogenous glutamate; an effect sensitive to SKF89976A and low-Na+-containing medium. Confocal microscopy shows that the GABA transporter GAT-1 is coexpressed with the vesicular glutamate transporter vGLUT-1 and with the plasma membrane glutamate transporter EAAT2 in a substantial portion of synaptosomal particles. The GABA effect was external Ca2+ independent and was not decreased when cytosolic Ca2+ ions were chelated by BAPTA. The glutamate transporter blocker DL-TBOA or dihydrokainate inhibited in part (approximately 35%) the GABA (10 microM)-evoked [3H]D-ASP release; this release was strongly reduced by the anion channel blockers niflumic acid and NPPB. GABA, up to 30 microM, was unable to augment significantly the basal release of [3H]glycine from spinal cord synaptosomes, indicating selectivity for glutamatergic transmission. It is concluded that GABA GAT-1 transporters and glutamate transporters coexist on the same spinal cord glutamatergic terminals. Activation of these GABA transporters elicits release of glutamate partially by reversal of glutamate transporters present on glutamatergic terminals and largely through anion channels.

Effect of a gamma-aminobutyric acid-enriched dairy product on the blood pressure of spontaneously hypertensive and normotensive Wistar-Kyoto rats.

We investigated the blood-pressure-lowering effects of gamma-aminobutyric acid (GABA) and a GABA-enriched fermented milk product (FMG) by low-dose oral administration to spontaneously hypertensive (SHR/Izm) and normotensive Wistar-Kyoto (WKY/Izm) rats. FMG was a non-fat fermented milk product produced by lactic acid bacteria, and the GABA contained in FMG was made from the protein of the milk during fermentation. A single oral dose of GABA or FMG (5 ml/kg; 0.5 mg GABA/kg) significantly (P<0.05) decreased the blood pressure of SHR/Izm from 4 to 8 h after administration, but did not increase that of WKY/Izm rats. The hypotensive activity of GABA was dose-dependent from 0.05 to 5.00 mg/kg in SHR/Izm. During the chronic administration of experimental diets to SHR/Izm, a significantly slower increase in blood pressure with respect to the control group was observed at 1 or 2 weeks after the start of feeding with the GABA or FMG diet respectively (P<0.05) and this difference was maintained throughout the period of feeding. The time profile of blood-pressure change due to administration of FMG was similar to that of GABA. FMG did not inhibit angiotensin 1-converting enzyme. Furthermore, an FMG peptide-containing fraction from reverse-phase chromatography lacked a hypotensive effect in SHR/Izm rats. The present results suggest that low-dose oral GABA has a hypotensive effect in SHR/Izm and that the hypotensive effect of FMG is due to GABA.

Effects of gamma-aminobutyric acid on action of gastrin-releasing peptidergic neurons in exocrine secretion of isolated, perfused rat pancreas.

gamma-Aminobutyric acid (GABA) has been reported to enhance exocrine secretion evoked by intrinsic neuronal excitation in the pancreas. To see the effect of GABA on the action of gastrin-releasing peptide (GRP)ergic neurons in exocrine secretion of the pancreas. Pancreatic neurons were excited by electrical field stimulation (EFS) in the isolated, perfused rat pancreas. GRP in the pancreatic circulation was neutralized by an anti-GRP antiserum to block GRPergic neuronal action on pancreatic exocrine secretion. GABA (3, 10, 30 microM), given intra-arterially, elevated the EFS-evoked pancreatic secretions of fluid and amylase dose-dependently. An anti-GRP antiserum (10 microL/mL: titer of 1:66,000) reduced the GABA (10 microM)-enhanced EFS-evoked pancreatic secretions. Synthetic porcine GRP-27 (30, 100, 300 p ) increased the pancreatic secretions dose-dependently, and these were further elevated by GABA (10 microM). The anti-GRP antiserum also reduced the GABA-enhanced GRP (100 p )-induced pancreatic secretions. Bicuculline (10 microM) reduced the enhancing effect of GABA on pancreatic secretions evoked by EFS as well as GRP. GABA enhances pancreatic secretions evoked by EFS as well as GRP, which is reduced by the anti-GRP antiserum. The enhancing effects of GABA on the EFS- and GRP-induced pancreatic secretions are diminished by bicuculline. The results indicate that GABA enhances intrinsic GRPergic neuronal action on exocrine secretion via the GABA(A) receptors in the rat pancreas.

Effects of GABAergic agents on anesthesia induced by halothane, isoflurane, and thiamylal in mice

The effects of γ-aminobutyric acid (GABA) receptor modulators and GABA uptake inhibitors on volatile and intravenous anesthetic-induced anesthesia were examined in male ICR mice, as assessed by the loss of righting reflex (LORR). The GABA uptake inhibitors, NO-711 and SKF89976A, which are permeable to the blood–brain barrier (BBB), but not nipecotic acid or guvacine, which poorly permeate BBB, shortened the onset of LORR but did not affect the duration of LORR induced by 1.5% halothane and 2% isoflurane. NO-711 and SKF89976A shortened the onset of and prolonged the duration of LORR induced by thiamylal (45 mg/kg ip). The GABA mimetics, muscimol and diazepam, shortened the onset of and prolonged the duration of LORR induced by halothane, isoflurane, and thiamylal. On the other hand, picrotoxin, a GABA A receptor antagonist, prolonged the onset of LORR induced by all anesthetics tested. Another GABA A receptor antagonist, bicuculline, prolonged the onset of LORR induced by halothane, but not by isoflurane or thiamylal. Both antagonists failed to affect the duration of LORR induced by halothane, isoflurane, or thiamylal. Baclofen, a GABA B receptor agonist, enhanced both volatile anesthetics- and thiamylal-induced anesthesia. These results suggest that anesthesia induced by volatile and intravenous anesthetics might be correlated with the modification of the pre- and/or postsynaptic GABAergic activities.

Effects of γ-aminobutyric acid on putative sympatho-excitatory neurons in the rat rostral ventrolateral medulla in vitro. Intracellular study

Neurons in the rat rostral ventrolateral medulla (RVLM) were electrophysiologically characterized and identified using an intracellular recording technique in vitro. The recorded neurons could be classified into three types: spontaneously active neurons with a regular pattern of action potential generation; spontaneously active neurons with an irregular pattern of discharge; and silent neurons. In regularly firing neurons during hyperpolarization below spike generation level there occurred: (a) a ‘resetting’ of regular pattern of firing; (b) the absence of underlying excitatory postsynaptic potentials; (c) an anomalous rectification that produced a decay in the hyperpolarization. In regularly firing neurons, γ-aminobutyric acid (GABA) (2–5 μM) produced a reversible membrane hyperpolarization, reduction of frequency of discharge and a moderate decrease in membrane input resistance. These effects were completely blocked in the presence of the GABAa antagonists bicuculline (16 μM) or picrotoxin (50 μM). However, the superfusion of bicuculline (16 μM), or picrotoxin (50 μM) alone elicited depolarization, increase in firing rate and increase of membrane input resistance. This study has provided evidence for regularly firing neurons in the RVLM in vitro, with strikingly similar electrophysiological characteristics to a group of neurons described in vivo as tonic sympathoexcitatory [8]. In vitro they are still modulated by gabaergic inputs acting predominantly upon GABAa receptors.

Some Features of NADP-Dependent Isocitrate Dehydrogenase Functioning in Pea Leaves upon Exposure to Salt Stress

In pea seedlings transferred to a medium containing 3% NaCl, NADP-dependent isocitrate dehydrogenase (NADP-IDH) activity in leaves increased more than twofold during the first hour, decreased, and increased again (approximately 1.5 times) by the 14th hour of exposure. Some catalytic and regulatory properties of NADP-IDH were studied using enzyme preparations purified from normal plants and plants exposed to salt stress. The results showed that Km for NADP-IDH in reactions with isocitrate and NADP decreased under stress by factors of 2 and 3, respectively. Specific features of enzyme activity regulation by citrate and trans-aconitate under these conditions were revealed. The inhibitory effects of γ-aminobutyric acid (GABA) and 2-oxoglutarate on NADP-IDH from plants exposed to salt stress was stronger than that on the enzyme from normal plants. Glutamine and glutamate slightly activated the enzyme in both cases.

Effects of gamma-aminobutyric acid on secretagogue-induced exocrine secretion of isolated, perfused rat pancreas.

Because GABA and its related enzymes have been determined in beta-cells of pancreas islets, effects of GABA on pancreatic exocrine secretion were investigated in the isolated, perfused rat pancreas. GABA, given intra-arterially at concentrations of 3, 10, 30, and 100 microM, did not exert any influence on spontaneous or secretin (12 pM)-induced pancreatic exocrine secretion. However, GABA further elevated CCK (10 pM)-, gastrin-releasing peptide (100 pM)-, or electrical field stimulation-induced pancreatic secretions of fluid and amylase dose dependently. The GABA (30 microM)-enhanced CCK-induced pancreatic secretions were completely blocked by bicuculline (10 microM), a GABA(A) receptor antagonist, but were not affected by saclofen (10 microM), a GABA(B) receptor antagonist. The enhancing effects of GABA (30 microM) on CCK-induced pancreatic secretions were not changed by tetrodotoxin (1 microM) but were partially reduced by cyclo-(7-aminoheptanonyl-Phe-D-Trp-Lys-Thr[BZL]) (10 nM), a somatostatin antagonist. In conclusion, GABA enhances pancreatic exocrine secretion induced by secretagogues, which predominantly induce enzyme secretion, via GABA(A) receptors in the rat pancreas. The enhancing effect of GABA is partially mediated by inhibition of islet somatostatin release.

Mg2+- ATPase in the fish brain and its ultrastructural localization

Effects of γ-aminobutyric acid (GABA) and ethanol on Mg2+-ATPase from mitochondrial and microsomal fractions of the fish brain were studied. GABA (10-8–10-4 M) activates microsomal Mg2+-ATPase, but has no effect on the mitochondrial enzyme activity. This effect of GABA on the microsomal Mg2+-ATPase was absent in the presence of 8% ethanol. Ethanol at 1– 10% concentrations inhibits the basal microsomal Mg2+-ATPase and has no effect on the mitochondria enzyme. Using cytochemical technique, Mg2+-ATPase was revealed both in neurons and in glial cells. The ethanol-sensitive Mg2+-ATPase is located in the area of synaptic junctions and is bound to plasma, vesicular, and smooth endoplasmic reticulum membranes.

GABA enhances short wavelength-sensitive cone input and reduces red cone input to carp L-type horizontal cells

Light responses of cone-driven horizontal cells were recorded intracellularly in the isolated superfused carp retina and the effects of γ-aminobutyric acid (GABA) on signals from red-sensitive (R-) and short-wavelength-sensitive (S-) cones (green cones and/or blue cones) were studied. In the presence of a bright red (694 nm) background light, which substantially suppressed signal from R-cones, the responses of L-type horizontal cells (L-HCs) to 532-nm flashes, predominantly driven by the S-cone input, were potentiated by application of GABA. In contrast, the responses of these cells to 694-nm flashes driven by the R-cone input, were suppressed, when signal from S-cones was suppressed by a bright 532-nm background light. Both the effects could be reversed by co-application of bicuculline, suggesting the involvement of GABA A receptors. It was unlikely that the potentiation by GABA of the S-cone driven responses of the L-HCs was mediated by actions of GABA on the cone photoreceptors. The dual action of GABA persisted in the dopamine-depleted retina, indicating no involvement of the dopaminergic interplexiform cells. We speculate that this dual action may be partially due to differential modulation by GABA of different postsynaptic mechanisms respectively mediating signal transfer from R-cones and S-cones to L-HCs.

Role of Potassium Channels in the GABA Inhibitory Action on the Purinergic Response to Electrical Field Stimulation in Rat Isolated Vas Deferens

The involvement of potassium channels in the GABAB receptor-mediated modulatory effects of γ-aminobutyric acid (GABA) on the purinergic response of rat isolated vas deferens exposed to electrical field stimulation (EFS) was investigated. Non-selective Ca2+-dependent K+ (KCa) channel antagonists, tetraethylammonium chloride (TEA) and 4-aminopyridine (4-AP), and a selective large conductance Ca2+-activated K+ (BK) channel antagonist, iberiotoxin, reduced the inhibitory effects of GABA on the purigenic response to EFS. The GABA induced-inhibition of the EFS contractions was not affected by the small conductance Ca2+-activated K+ (SK) channel blocker, apamin, or by the ATP-sensitive K+ channel (KATP) channel blocker, glibenclamide. These observations seem to indicate a coupling between GABAB receptors and BK channels in rat vas deferens.

Comparison of γ-aminobutyric acid effects in different parts of the cat ileum

The effects of γ-aminobutyric acid (GABA) and those of a GABA A (muscimol) and a GABA B (baclofen) receptor agonists were determined on the spontaneous activity of longitudinally or circularly oriented preparations (segments) isolated from terminal, proximal and distal parts of the cat ileum. GABA applied at 1 μM to 2 mM caused dose-dependent biphasic changes (relaxation and contraction) in spontaneous activity of the longitudinal and circular layers in the terminal and distal parts of the cat ileum and monophasic changes (contraction) in the proximal part. The potency of GABA to elicit relaxant and/or contractile effects in different parts of the ileum showed a proximal-to-terminal increasing pattern. In the longitudinal layer of the distal and terminal ileum, muscimol (100 μM) mimicked the relaxation phase of the GABA effect, while baclofen (100 μM) simulated the contractile phase. Bicuculline, atropine and tetrodotoxin abolished GABA- and muscimol-induced relaxation and suppressed, but failed to prevent GABA- and baclofen-induced contractions. In addition, 2-hydroxysaclofen antagonized the baclofen-induced contractile effect, reduced the GABA-induced contractile phase but failed to prevent GABA- and muscimol-induced relaxation. In the circular layer of the same regions, muscimol mimicked the biphasic GABA effects, while baclofen was without effect. Bicuculline, atropine and tetrodotoxin completely prevented the GABA- and muscimol effects, while 2-hydroxysaclofen failed to antagonize them. In the longitudinal and circular layers of the proximal ileum, muscimol (100 μM) exerted a `GABA-like' transient contractile effect, while baclofen (100 μM) did not elicit any response. Bicuculline, atropine and tetrodotoxin antagonized the GABA- and muscimol-induced contractile responses of longitudinal and circular layers, while 2-hydroxysaclofen was ineffective. The results suggested that the inhibitory and/or excitatory action of GABA on cholinergic transmission in different regions of cat ileum varies along an increasing gradient towards the terminal ileum and is mediated by GABA A and GABA B receptors in the terminal and distal ileum and by GABA A receptors in the proximal ileum.

GABA-evoked depolarisations in the rat cortical wedge: involvement of GABA A receptors and HCO 3− ions

The effect of γ-aminobutyric acid (GABA) was investigated on cortical wedges prepared from male Sprague–Dawley rats. GABA evoked concentration-dependent depolarisations (EC 50: 0.8 mM), which were attenuated by up to 60% when bicarbonate-buffered aCSF was replaced with HEPES-buffered aCSF. Responses to 1 mM GABA were attenuated by (−)-bicuculline and picrotoxin and were potentiated by chlordiazepoxide and pentobarbitone. Ionotropic glutamate receptor antagonists had no effect. We conclude that GABA-evoked depolarisations are mediated via GABA A receptors, arising in part from HCO 3 − efflux from cells.