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J C Szerb

Publications and source records attributed to J C Szerb.

At least 37 records · Page 2Linked to original sources
PubMed1984

Storage and release of endogenous and labelled GABA formed from [3H]glutamine and [14C]glucose in hippocampal slices: effect of depolarization.

To study the effect of depolarization on the synthesis, storage and release of GABA, hippocampal slices were incubated in 0.25 mM [3H]glutamine and 2.5 mM [14C]glucose in the presence of 3 or 50 mM K+. Total and labelled glutamine, glutamate and GABA contents were measured by high-performance liquid chromatography. Depolarization in the presence of Ca2+ led to a two-fold increase of labelled glutamate and a 3-fold increase of labelled GABA content originating from both labelled precursors. In the absence of Ca2+ and in the presence of 10 mM Mg2+, depolarization failed to increase labelled glutamate content and labelled GABA formation was increased by only 30%. Following superfusion with unlabelled 0.25 mM glutamine and 2.5 mM glucose a second depolarization with 50 mM K+ released twice as much labelled GABA from slices that had been incubated in the presence of 50 mM K+, than from those incubated in 3 mM K+. This difference remained unchanged in slices that were superfused with 1 mM aminooxyacetic acid, an inhibitor of GABA synthesis. The contribution of labelled GABA, especially of GABA derived from [3H]glutamine, to released GABA was significantly higher than to GABA stored in the slices. Results suggest that depolarization in the presence of Ca2+ results in increased glutamate and GABA synthesis from both glutamine and glucose and that part of GABA released by high K+ originates from preformed GABA stores.

Aminooxyacetic Acid↗
PubMed1984

Bilateral ablation of the corticostriatal projection: behavioral, biochemical and electrophysiological correlates.

Striatal neuronal responses to dexamphetamine, 2.5 mg/kg i.p., were examined in normal and bilateral cortically ablated freely moving rats using multiunit recording. Striatal glutamate levels, D1 and D2 receptor binding, and haloperidal catalepsy were examined in both sham-operated and ablated animals. Bilateral ablation of the cortex, while not affecting dexamphetamine-induced behavioral activation, changed the striatal neuronal response from predominantly excitation to inhibition. Striatal glutamate levels were reduced 22% in ablated animals; and dopamine D-2 receptor binding sites were similarly decreased by 20%. In bilaterally ablated animals, haloperidol-induced catalepsy was greatly reduced.

Animals↗
PubMed1984

Glutamine enhances glutamate release in preference to gamma-aminobutyrate release in hippocampal slices.

To see the effect of physiological concentrations of glutamine on glutamate and gamma-aminobutyrate (GABA) release, rat hippocampal slices were incubated and (or) superfused without or with 0.25 mM glutamine in the presence or absence of Ca2+. The spontaneous and high K+-evoked release of glutamine, glutamate, and GABA was measured by precolumn derivatization and reversed phase high performance liquid chromatography. The spontaneous release of glutamate was increased by superfusion with glutamine and this increase was three times greater in the absence than in the presence of Ca2+. Spontaneous GABA release was not increased by glutamine. While in the absence of glutamine, the release of glutamate and GABA evoked by 50 mM K+ was about equal, in the presence of glutamine the evoked release of glutamate was nearly three times greater than that of GABA. The large evoked release of glutamate in the presence of glutamine was Ca2+ dependent nearly to the same extent as the smaller evoked release in the absence of glutamine. Results suggest that the availability of extracellular glutamine regulates the release of glutamate but not of GABA. Extracellular Ca2+ controls the spontaneous conversion of glutamine to glutamate but the site and mechanism of this control is uncertain.

Amino Acids↗
PubMed1983

The release of [3H]GABA formed from [3H]glutamate in rat hippocampal slices: comparison with endogenous and exogenous labeled GABA.

to compare the storage and release of endogenous GABA, of [3H]GABA formed endogenously from glutamate, and of exogenous [14C]GABA, hippocampal slices were incubated with 5 microCi/ml [3,4-3H]1-glutamate and 0.5 microCi/ml [U-14C]GABA and then were superfused in the presence or absence of Ca+ with either 50 mM K+ or 50 microM veratridine. Endogenous GABA was determined by high performance liquid chromatography which separated labeled GABA from its precursors and metabolites. Exogenous [14C]GABA content of the slices declined spontaneously while endogenous GABA and endogenously formed [3H]GABA stayed constant over a 48 min period. In the presence of Ca+ 50 mM K+ and in the presence or absence of Ca2+ veratridine released exogenous [14C]GABA more rapidly than endogenous or endogenously formed [3H]GABA, the release of the latter two occurring always in parallel. The initial specific activity of released exogenous [14C]GABA was three times, while that of endogenously formed [3H]GABA was only 50% higher than that in the slices. There was an excess of endogenous GABA content following superfusion with 50 mM K+ and Ca2+, which did not occur in the absence of Ca2+ or after veratridine. The observation that endogenous GABA and [3H]GABA formed endogenously from glutamate are stored and released in parallel but differently from exogenous labelled GABA, suggests that exogenous [3H] glutamate can enter a glutamate pool that normally serves as precursor of GABA.

Animals↗
PubMed1982

Turnover and release of GABA in rat cortical slices: effect of a GABA-T inhibitor, gabaculine.

The turnover and release of endogenous and labeled GABA were followed in rat cortical slices after incubation with [3H]GABA. High performance liquid chromatography was used to measure endogenous GABA and to separate [3H]GABA from its metabolites. During superfusion with 3 mM K+ the slices rapidly lost their [3H]GABA content while maintaining constant GABA levels. Exposure to 50 mM K+ for 25 min caused an initial rapid rise in the release of both endogenous and [3H]GABA followed by a more rapid decline in the release of the latter. The specific activity of released GABA was two to four times higher than that in the slices. Depolarization lead to a net synthesis of GABA. The GABA -T inhibitor, gabaculine, (5 micrometers) in vitro arrested the metabolism of [3H]GABA and rapidly doubled the GABA content but did not significantly increase the high K+ evoked release of endogenous GABA. In vivo pretreatment with 0.5 mM/kg gabaculine quadrupled GABA content and increased both the spontaneous and evoked release of endogenous GABA but while its Ca2+ -dependent release increased by 50%, the Ca2+ -independent release was enhanced sevenfold. This large Ca2+ -independent release of GABA is likely to have different functional significance from the normal Ca2+ -dependent release.

4-Aminobutyrate Transaminase↗
PubMed1981

Compartments of labeled and endogenous gamma-aminobutyric acid giving rise to release evoked by potassium or veratridine in rat cortical slices.

To establish compartments involved in depolarization-induced release of gamma-aminobutyric acid (GABA) in rat brain slices, the amount of exogenous labeled and endogenous GABA released and retained was followed during 48 min exposure to 50 mM-K+ or to 50 microM-veratridine. Endogenous GABA was measured with high performance liquid chromatography. The presence of 10 microM-aminooxyacetic acid throughout prevented both the metabolism of GABA and the formation of endogenous GABA due to depolarization. During superfusion with 50 mM-K+ and 2.6 nM-Ca2+ the efflux of labeled and endogenous GABA after an initial large increase declined to 10% of the highest value with constant and identical rates. Kinetic analysis of efflux showed that 10% of endogenous and 25% of labeled GABA present is available for release by high K+ and Ca2+. In the absence of Ca2+, release by high K+ of both labeled and endogenous GABA was nearly suppressed. Veratridine, unlike high K+, caused an efflux which declined with an initial fast and late very slow phase. The slow efflux by veratridine was doubled in the absence of Ca2+. Exposure to veratridine in the absence of Ca2+ during 120 min released nearly 70% of labeled and endogenous GABA present. Results suggest that only about 0.25 mumol . g-1 endogenous GABA is the source of physiological Ca2+-dependent release, while much of the remaining GABA present is released only under unphysiological conditions.

Animals↗
PubMed1980

Kinetics of morphine-sensitive [3H]-acetylcholine release from the guinea-pig myenteric plexus.

1 Longitudinal muscle-myenteric plexus preparations from the guinea-pig ileum were superfused at a constant rate while isotonic contractions were monitored. 2 The preparations were superfused with [3H]-choline while stimulated supramaximally at 0.1 Hz followed by washout in the presence of hemicholinium-3. The evoked release of the label due to a second 0.1 Hz stimulation in the absence of an anticholinesterase was measured. 3 Evoked efflux of the label was initially fast followed by a slower phase. 4 Morphine reduced the size of the pool and the rate of the initial fast efflux and the size of the pool but not the rate of the slow efflux evoked by supramaximal stimulation. 5 Submaximal stimulation reduced only the size of the pools from which the fast and slow efflux originated. 6 Naloxone reversed the depression of contractions and evoked release produced by morphine. 7 Results suggest that 0.1 Hz stimulation releases [3H]-acetylcholine simultaneous from two pools. The fast release may originate from spontaneously firing units whose rate of discharge is depressed by morphine, while the slow release originates from neurones which do not fire spontaneously and whose threshold to field stimulation is increased by morphine.

Acetylcholine↗
PubMed1977

Release of [3H]acetylcholine from rat hippocampal slices: effect of septal lesion and of graded concentrations of muscarnic agonists and antagonists.

To establish the existence and sensitivity of presynaptic muscarinic receptors on central cholinergic neurons, the electrically evoked release of [3H]ACh from hippocampal slices was measured after medial septal lesion or in the presence of graded concentrations of muscarinic agonists and antagonists. One week after septal lesion, the evoked release of [3H]ACh was abolished, indicating that septo-hippocampal cholinergic fibres are the source of this release. The muscarinic agonists, Oxotremorine, carbamylcholine and arecoline reduced the rate of evoked release of [3H]ACh with an ED50 similar to the ED50 required to displace specific [3H]quinuclidinyl benzilate (QNB) binding as found by Yamamura and Snyder. However, the antagonists QNB, antropine and scopolamine were 10 times weaker in increasing the rate of [3H]ACh release than in displacing [3H]QNB binding. Results suggest that the lower affinity of muscarinic antagonists to presynaptic receptors prevents the demonstration of the specific labelling of these receptors with [3H]QNB.

Acetylcholine↗
PubMed1977

The effect of cholinergic drugs on [3H]acetylcholine release from slices of rat hippocampus, striatum and cortex.

Slices from rat hippocampus, striatum or cortex were incubated with l mum [3H] choline and following 75 min superfusion with Krebs solution the efflux of radioactivity was measured. The slices were stimulated either electrically (1 Hz) or with 25 mM potassium and the rate constant of the evoked release and the size of the releasable pool were estimated. The spontaneous efflux of radioactivity and the releasable pool but not the rate of evoked release correlated with the reported endogenous ACh content of the 3 areas. Raised potassium released radioactivity at a lower rate but from a larger pool than electrical stimulation from all 3 areas. In all 3 areas atropine alone potentiated while physostigmine, oxotremorine and carbamylcholine decreased the rate of evoked release. This depression was fully antagonized by atropine. The drugs had no effect on the size of the releasable pool. Findings suggest that muscarinic receptors located on cholinergic axons or terminals have a physiological role in the autoregulation of ACh release from these 3 areas.

Acetylcholine↗
PubMed1976

Acetylcholine release from visual and sensorimotor cortices of conditioned rabbits: the effects of sensory cuing and patterns of responding.

A technique was devised for the collection of acetylcholine (ACh) released from the cerebral cortex of awake rabbits while they were performing a previously learned operant task. Based on the assumption that ACh release is directly proportional to the activity of cholinergic synapses under the area of collection, two hypotheses of the functional role of cortical cholinergic mechanisms were examined: (1) that activity in cholinergic neurons is related to the inhibition of responding; (2) that cholinergic activity is related to the perception of a 'significant' stimulus. Five groups trained on different behavioral paradigms were used to test these hypotheses. ACh release was collected concurrently from visual and sensorimotor cortices to differentiate diffuse from specific cortical effects. A small (50-100%) increase in ACh release was found in all groups and from both cortical areas. In the case of one group (visually cued, reinforced for low response rates) a significantly greater increase occurred from sensorimotor cortex only. These findings do not support either hypothesis alone, and are interpreted as evidence for two cholinergic systems within, or projecting to the cortex. One is related to generalized behavioral arousal and desynchronization of the electroencephalogram. Activation of the second cholinergic system is dependent on both response inhibition and the presence of a significant stimulus of the visual (but not of the auditory) modality.

Acetylcholine↗
PubMed1976

Storage and release of labelled acetylcholine in the myenteric plexus of the guinea-pig ileum.

Guinea-pig ileum myenteric plexus-longitudinal muscle preparation was superfused with [3H]choline for 15 min either without being stimulated or during field stimulation at 0.1 or 16 Hz; the preparation was then either removed immediately or after 75- or 135-min superfusion with hemicholinium-3 (HC-3) and the total acetylcholine (ACh) and [3H]ACh contents were determined. For measuring the release of [3H]ACh the preparation was stimulated for 60 min the second time at 0.1 or 16 HZ in the presence of hemicholinium. Exposure to [3H]choline without stimulation resulted in the formation of [3H]ACh stores which were maintained in the first 75 min but decreased therafter. Labelling during stimulation at 16 Hz produced the largest and best maintained [3H]ACh content. Following labelling during 0.1-Hz stimulation, more label could be released than following labelling in the absence of stimulation. Labelling during 16-Hz stimulation did not increase any further in fool of [3H]ACh accessible to release by 0.1-Hz stimulation, but caused a 2.5 times increase in the pool from which Hz stimulation released [3H]ACh. These results suggest that two populations of cholinergic neurons exist in the myenteric plexus, one activated only by high frequency stimulation, the other by both high and low frequency stimulation.

Acetylcholine↗