The spontaneous and evoked release of newly synthesized [14C]GABA from rat cerebral cortex, in vitro

Gauchy, C.; Iversen, Leslie L.; Jessell, Thomas M.

doi:10.1016/0006-8993(77)90756-9

Cited by 22 publications

(4 citation statements)

References 18 publications

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“…The INH-induced decrease in the amount of GABA released by the Ca2+-dependent mechanism, with no concomitant change in the amount of GABA provided by Ca2+-independent release, suggests that endogenous synthesis of GABA supplies only the Ca2+-dependent pool. This proposal is also compatible with the finding of Gauchy et al (1977) that newly synthesized GABA was preferentially released by a Ca"-dependent mechanism.…”

Section: Compartmentation Of Gaba Metabolism In Synaptosomessupporting

confidence: 91%

γ‐Aminobutyric Acid Release from Synaptosomes Prepared from Rats Treated with Isonicotinic Acid Hydrazide and Gabaculine

Wood

Kurylo

Lane

1988

Journal of Neurochemistry

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The potassium-stimulated release of gamma-aminobutyric acid (GABA) from synaptosomes was determined in preparations from control rats and from rats treated with a convulsant agent [isonicotinic acid hydrazide (INH)] and an anticonvulsant agent (gabaculine). INH treatment brought about a significant decrease in Ca2+-dependent release of GABA with no effect on Ca2+-independent release, whereas gabaculine caused an increase in Ca2+-independent release with no effect on Ca2+-dependent release of GABA. Thus, the anticonvulsant action of gabaculine was not a simple reversal of the effects of INH on GABA release. The results indicate that there are at least two pools of GABA in nerve endings and support the hypothesis that exogenous GABA is taken up first into a pool that supplies GABA for Ca2+-independent release and then is transferred to a second pool (Ca2+-dependent releasable), where it mixes with newly synthesized GABA.

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Section: Compartmentation Of Gaba Metabolism In Synaptosomessupporting

confidence: 91%

γ‐Aminobutyric Acid Release from Synaptosomes Prepared from Rats Treated with Isonicotinic Acid Hydrazide and Gabaculine

Wood

Kurylo

Lane

1988

Journal of Neurochemistry

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“…I n isolated synaptic terminals (synaptosomes) GABA is located in both the cytoplasm and vesicles (KrnjeviC and Whittaker, 1965; De Belleroche and Bradford, 1977). Different labeled precursors are incorporated to a different extent into GABA located in various compartments (Minchin, 1977;Gauchy et al, 1977). About 10% of GABA present has a much faster turnover rate than the rest (Garfinkel, 1970).…”

mentioning

confidence: 99%

Compartments of Labeled and Endogenous γ‐Aminobutyric Acid Giving Rise to Release Evoked by Potassium or Veratridine in Rat Cortical Slices

Szerb

Ross

Gurevich

1981

Journal of Neurochemistry

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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.

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“…The release of GABA from superfused tissues, glial cells, brain and spinal cord slices and synaptosomes has been studied extensively in recent years (90)(91)(92)(93)(94)(95)(96). There have been, however, conflicting data as to whether the release is calcium-dependent and whether certain forms of stimulation (i.e.…”

Section: Gaba Releasementioning

confidence: 99%

Pharmacology of GABA-mediated inhibition of spinal cord neurons in vivo and in primary dissociated cell culture

Macdonald

Young

1981

Mol Cell Biochem

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In this paper it is shown that the postsynaptic GABA-receptor chloride ion channel complex is composed of several functional subunits. There are probably at least two stereospecific locations on the receptor for GABA-binding and both must be occupied to obtain an increase in chloride conductance. The interaction between these sites is uncertain but there could be either positive cooperativity between the sites or only a requirement that both sites are occupied without occupation of either site affecting the affinity for GABA of the other site. There is a chloride conductance channel coupled to the GABA receptor which opens for an average of 20 msec and has an average conductance of 18 pS. The GABA-coupled chloride channel may or may not have the same composition as the glycine coupled chloride channel. In addition to the GABA-recognition site and the chloride ion channel, GABA-receptors must have additional binding sites or modulator sites where drugs can bind to modify GABA activation of the GABA receptor. The convulsant PICRO binds to a site which is independent of the GABA site and PICRO reduces GABA responses. Barbiturates and benzodiazepines augment GABA-responses without reducing GABA-binding and thus they must bind to a modulator site independent of the GABA recognition site. Whether or not this is the same site as the PICRO binding site is uncertain. Thus, the GABA-receptor-chloride ion channel complex is composed of at least: 1) two GABA-binding sites; 2) a chloride ion channel; 3) a convulsant binding site (PICRO-binding site) and 4) an anticonvulsant binding site. This organization serves several obvious purposes. First, since two GABA-molecules are required to activate GABA-coupled chloride ion channels, the dose-response relationship for GABA is sigmoidal and steep. Thus minor shifts in GABA affinity will produce large alterations in GABA-responses and the GABA receptor can be easily modulated. Second, since the receptors has binding sites for convulsant and anticonvulsant compounds which decrease and increase GABA-responses, GABAergic inhibition can easily be modulated.

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The spontaneous and evoked release of newly synthesized [14C]GABA from rat cerebral cortex, in vitro

Cited by 22 publications

References 18 publications

γ‐Aminobutyric Acid Release from Synaptosomes Prepared from Rats Treated with Isonicotinic Acid Hydrazide and Gabaculine

γ‐Aminobutyric Acid Release from Synaptosomes Prepared from Rats Treated with Isonicotinic Acid Hydrazide and Gabaculine

Compartments of Labeled and Endogenous γ‐Aminobutyric Acid Giving Rise to Release Evoked by Potassium or Veratridine in Rat Cortical Slices

Pharmacology of GABA-mediated inhibition of spinal cord neurons in vivo and in primary dissociated cell culture

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