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1.
The release of [3H]GABA from superfused slices of rat cerebral cortex was investigated in the presence and absence of the GABA-transaminase inhibitor aminooxyacetic acid (AOAA). In the latter case, an ion-exchange column chromatographic technique was used to separate [3H]GABA from tritiated metabolites released with it into the superfusate. In the absence of AOAA, omission of Ca2+ from the superfusion medium reduced the release of [3H]GABA evoked by a 30 mM K+ pulse by 81.6%, whereas in comparable experiments carried out in the presence of AOAA omission of Ca2+ reduced the K+-evoked release by only 23.5%. Similar results were obtained when a 50 mM K+ pulse was used, where-upon omission of Ca2+ reduced [3H]GABA release by 78.7% in the absence of AOAA as compared with a reduction of only 47.9% when AOAA was present. It is concluded that the presence of AOAA decreases the Ca2+-dependence of K+-evoked [3H]GABA release in this system. 相似文献
2.
Release of [3H]noradrenaline from rat hippocampal synaptosomes was triggered by pulses of 25 mM K+, 5 μM veratridine or superfusion with the Ca2+ ionophore A23187. GABA with bicuculline or chlordiazepoxide depressed the release of [3H]noradrenaline evoked by depolarisation but not by the Ca2+ ionophore. 8 Br-cAMP with [Ca2+]0 0.3 mM had no effect on spontaneous or K+-evoked release of [3H]noradrenaline and completely blocked the effect of chlordiazepoxide and GABA with bicuculline. With [Ca2+]0 1 mM 8 Br-cAMP enhanced spontaneous and K+-evoked release of [3H]noradrenaline, and reversed the depression caused by GABA with bicuculline. GABA alone evoked Ca2+-dependent release of [3H]noradrenaline which was sensitive to [Cl?]0. The results suggest that the GABAA-receptor mediated release of [3H]noradrenaline is due to depolarisation resulting from increased Cl? conductance whereas the depression of depolarisation-dependent release of [3H]noradrenaline by GABAB or benzodiazepine receptors is mediated by a cAMP-dependent decrease in the voltage-dependent Ca2+ conductance. 相似文献
3.
J. B. Lombardini 《Neurochemical research》1993,18(2):193-202
The effects of spontaneous and evoked [3H]taurine release from a P2 fraction prepared from rat retinas were studied. The P2 fraction was preloaded with [3H]taurine under conditions of high-affinity uptake and then examined for [3H]taurine efflux utilizing superfusion techniques. Exposure of the P2 fraction to high K+ (56 mM) evoked a Ca2+-independent release of [3H]taurine. Li+ (56 mM) and veratridine (100 M) had significantly less effect (8–15% and 15–30%, respectively) on releasing [3H]taurine compared to the K+-evoked release. 4-Aminopyridine (1 mM) had no effect on the release of [3H]taurine. The spontaneous release of [3H]taurine was also Ca2+-independent. When Na+ was omitted from the incubation medium K+-evoked [3H]taurine release was inhibited by approximately 40% at the first 5 minute depolarization period but was not affected at a second subsequent 5 minute depolarization period. The spontaneous release of [3H]taurine was inhibited by 60% in the absence of Na+. Substitution of Br– for Cl– had no effect on the release of either spontaneous or K+-evoked [3H]taurine release. However, substitution of the Cl– with acetate, isethionate, or gluconate decreased K+-evoked [3H]taurine release. Addition of taurine to the superfusion medium (homoexchange) resulted in no significant increase in [3H]taurine efflux. The taurine-transport inhibitor guanidinoethanesulfonic acid increased the spontaneous release of [3H]taurine by approximately 40%. These results suggest that the taurine release of [3H]taurine is not simply a reversal of the carrier-mediated uptake system. It also appears that taurine is not released from vesicles within the synaptosomes but does not rule out the possibility that taurine is a neurotransmitter. The data involving chloride substitution with permeant and impermeant anions support the concept that the major portion of [3H]taurine release is due to an osmoregulatory action of taurine while depolarization accounts for only a small portion of [3H]taurine release. 相似文献
4.
John C. Szerb 《Neurochemical research》1982,7(2):191-204
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 M) 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. 相似文献
5.
On homogenization of rat cerebral cortex slices previously incubated with [3H] GABA or [14C]GABA for 5 or 30 min, respectively, particles were recovered in P2 fractions which exhibited similar buoyant density, but different sedimentation velocity on linear sucrose density gradient centrifugation. The K+-evoked release of [3H]GABA from particles isolated from slices previously incubated for 5 min with [3H]GABA was increased in the presence of exogenous Ca2+. In contrast, the K+-evoked release from particles isolated from slices previously incubated for 30 min with [3H]GABA, was not influenced by the presence of exogenous Ca2+.These results suggest that, depending on the incubation time of slices, exogenously applied GABA can be detected in differnnt pools. These pools not only seem to differ in their Ca2+ dependency of K+-evoked release but also in their subcellular localization. 相似文献
6.
A possible role for protein kinases in the regulation of GABA exocytosis in nerve endings was investigated. The effect on the release of the radioactive neurotransmitter ([3H]GABA) from mouse brain synaptosomes of several protein kinase inhibitors was estimated after treatment with 37 mM K+ in the absence of external Na+, a condition under which [3H]GABA release is completely Ca2+ dependent. Among the inhibitors one group inhibit the kinases by binding to the catalytic site (i.e. staurosporine and H7) and others (TFP, sphingosine and W7) act on the regulatory site of protein kinases. The compounds of the second group, which are reported to inhibit calmodulin dependent events and the increase in cytosolic Ca2+ (Ca
i
) induced by high K+ depolarization, were the most efficient inhibitors of [3H]GABA release. The selective inhibitor of CaMPK II, KN-62, also markedly diminished [3H]GABA release as well as the increase in Ca
i
induced by high K+. The kinase inhibitors from the first group that are unable to diminish the increase in Ca
i
induced by high K+ were also less efficient inhibitors of [3H]GABA release even at high concentrations. The present results indicate that at the doses tested all the drugs inhibit to some extent the release of the Ca2+ dependent fraction of [3H]GABA perhaps by inhibiting a CaMPK II mediated phosphorylation step triggered by depolarization and facilitated by the elevation of Ca
i
. In addition, the second group of antagonists and KN-62 inhibit the elevation of Ca
i
to high K+ thus exhibiting a higher efficiency on [3H]GABA release than the first group of antagonists. 相似文献
7.
Jerzyk W. Lazarewicz Victor Leu Grace Y. Sun Albert Y. Sun 《Neurochemistry international》1983,5(4):471-478
Rat brain synaptosomes prelabeled with [14C]arachidonate in their phospholipids were superfused with well oxygenated Krebs-Ringer-bicarbonate solution containing 0.2% BSA and subsequently depolarized by elevating the K+ concentration in the superfusion medium from 5 to 55 mM. The efflux of labeled arachidonate at steady state was 0.19% (n = 12) of total radioactivity per min. In the presence of 2.5 mM Ca2+, high K+ (55 mM) in the medium elicited an increase in arachidonate efflux which amounted to 121.4% (n = 6) of control. Both Ca2+ and BSA were required for the stimulated efflux of arachidonate during K+-depolarization. Under the same condition, K+-stimulation also evoked the release of [3H]norepinephrine which was preloaded into the synaptosomes prior to superfusion. EGTA abolished the stimulated release of both arachidonate and norepinephrine during K+-depolarization. These results, together with the loss of labeled arachidonic acid from phospholipids (Majewska and Sun, 1982), indicate that deacylation of membrane lipids is involved in synaptic functions. 相似文献
8.
The effect of -Aga IVA, a P-type Ca2+ channel blocker, on the release of the inhibitory neurotransmitter GABA and on the elevation of Cai induced by depolarization was investigated in [3H]GABA and fura-2 preloaded mouse brain synaptosomes, respectively. Two strategies (i.e. 20 mM external K+ and veratridine) that depolarize by different mechanisms the preparation were used. High K+ elevates Cai and induces [3H]GABA release in the absence of external Na+ and in the presence of TTX, conditions that abolish veratridine induced responses. The effect of -Aga IVA on the Ca2+ and Na+ dependent fractions of the depolarization evoked release of [3H]GABA were separately investigated in synaptosomes depolarized with high K+ in the absence of extermal Na+ and with veratridine in the absence of external Ca2+, respectively. The Ca2+ dependent fraction of the evoked release of [3H]GABA and the elevation of Ca2+ induced by high K+ are markedly inhibited (about 50%) in synaptosomes exposed to -Aga IVA (300 nM) for 3 min before depolarization, whereas the Na+ dependent, Ca2+ independent carrier mediated release of [3H]GABA induced by veratridine, which is sensitive to verapamil and amiloride, is not modified by -Aga IVA. Our results indicate that an -Aga IVA sensitive type of Ca2+ channel is highly involved in GABA exocytosis. 相似文献
9.
The effects of external pH (pH
out) variations on the Na+ and on the Ca2+ dependent fractions of the evoked amino acid neurotransmitter release were separately investigated, using GABA as a model transmitter. In [3H]GABA loaded mouse brain synaptosomes, the external acidification (pH
out6.0) markedly decreased the Na+ dependent fraction of [3H]GABA release evoked by veratridine (10 M) in the absence of external Ca2+, as well as the Ca2+ dependent fraction of [3H]GABA release evoked by high (20 mM) K+ in the absence of external Na+. The depolarization-induced elevation of [Na
i
] (monitored in synaptosomes loaded with the Na+ indicator dye, SBFI) and the depolarization-induced elevation of [Ca
i
] (monitored in synaptosomes loaded with the Ca2+ indicator dye fura-2) were also markedly decreased at pH
out 6. On the contrary, the external alkalinization (pH
out 8) facilitated all the above responses. A slight increase of the baseline release of the [3H]GABA was observed when pH
out was changed from 7.4 to 8. This effect was only observed in the presence of Ca2+. pH
out changes from 7.4 to 6 or to 7 did not modify the baseline release of the transmitter. All the effects of pH
out variations on [3H]GABA release were independent on the presence of HCO-3. It is concluded that external H+ regulate amino acid neurotransmitter release by their actions on presynaptic Na+ channels, as well as on presynaptic Ca2+ channels. 相似文献
10.
The release of [3H]noradrenaline from rat hippocampal synaptosomes by 25 mM K+ and 5 μM veratridine, but not by the Ca2+ ionophore A23187 was depressed by baclofen. This depression was reversed by 8-Bromo-cAMP. This action of baclofen was stereospecific and mimicked both that of GABA in the presence of bicuculline and that of clonidine. The α2-adrenoceptor antagonists yohimbine and Wy25309 antagonised the action of clonidine and baclofen but not that of GABA. Specific binding of [3H]clonidine was displaced by Wy25309 and baclofen, but not by GABA. Specific binding of [3H]GABA in the presence of Ca2+ was displaced by baclofen but not by Wy25309. It is concluded that baclofen is not a specific agonist at GABAB receptors in the brain. 相似文献
11.
The effect of a protein kinase inhibitor, staurosporine, on Ca2+-dependent and Ca2+-independent release of [14C]GABA in isolated rat brain synaptosomes was studied. Calcium-dependent [14C]GABA release was stimulated by depolarization with a K+ channel blocker, 4-aminopyridine (4-AP), or high K+ concentration. It has been shown that the effect of 4-AP is Ca2+-dependent, while high K+ is able to evoke [14C]GABA release in both Ca2+-dependent and Ca2+-independent manners. In addition, Ca2+-independent [14C]GABA release was studied using α-latrotoxin (LTX) as a tool. Pretreatment of synaptosomes with staurosporine resulted in
pronounced inhibition of 4-AP-stimulated Ca2+-dependent [14C]GABA release. The inhibitory effect of staurosporine on [14C]GABA release was not due to modulation of 4-AP-promoted45Ca2+ influx into synaptosomes. If the process of [14C]GABA release occurred in the Ca2+-independent manner irrespectively of what, LTX or high K+, stimulated this process, it was not inhibited by staurosporine. Considering the above findings, it is reasonable to assume
that the absence of Ca2+ in the extracellular medium created conditions for activation of the process of neurotransmitter release without Ca2+-dependent dephosphorylation of neuronal phosphoproteins; as a consequence, regulation of exocytotic process was modulated
in such a manner that inhibition of protein kinases did not disturb exocytosis. 相似文献
12.
The effect of veratridine on neurotransmitter release was studied using rat brain synaptosomes superfused at 37°C. Veratridine (5–75 M) caused a concentration-dependent release of [3H]GABA from prelabeled synaptosomes in the presence of 2.7 mM Ca2+. In the whole range of veratridine concentrations, the release of [3H]GABA elicited by the drug was substantially increased rather than decreased in the absence of Ca2+ or with Ca2+ concentrations of 0.45 and 0.9 mM. The release of the amino acid was inhibited more by 5.4 mM than by 2.7 mM Ca2+. The effect on endogenous (chemically measured) GABA was similar to that on [3H]GABA. The inhibitory effect of Ca2+ on the veratridine-induced release of [3H]GABA was consistently seen in a variety of experimental conditions except one, namely when the experiment was run at room temperature (22–23°C) rather than at physiological temperature (37°C). In fact, at 22–23°C the release of GABA evoked by the alkaloid was somewhat potentiated by Ca2+. At 37°C, glutamate appeared to behave similarly to GABA, whereas the veratridine-induced release of [3H]noradrenaline and [3H]dopamaine was largely Ca2+-dependent. The mechanism of the release of transmitters elicited by veratridine is discussed. It is concluded that the evoked release of GABA and glutamate is due more to the veratridine-induced depolarization (Na+ influx) than to the accompanying influx of Ca2+, and it is suggested that the inhibitory effect of Ca2+ on the overall release of amino acids is due to the antagonism exerted by the divalent cation on the veratridine action at the Na+ channel. In contrast, in the case of catecholamines, the influx of Ca2+ would have a prominent role in triggering exocytotic release, whereas the depolarization itself would have slight or no importance. 相似文献
13.
Abstract— It has been reported that the release of GABA by high K+ is Ca2+-dependent while release induced by veratridine or electrical stimulation has been frequently found to be independent of Ca2+. To see the source of Ca2+-dependent and independent release of GABA, cortical slices which had accumulated [3H]GABA were exposed to 50 mm -K+ or 50 μm -veratridine for 48min. In the presence of Ca2+ the 2 agents released approx the same amount of [3H]GABA but tetrodotoxin (TTX) abolished release induced only by veratridine, while omission of Ca2+ reduced release induced only by 50mm -K+. Pre-exposure of the slices for 48min to 50mm -K+ in the presence of Ca2+ reduced the second release by 50mm -K+ by 77% and that by veratridine by 74%, suggesting that in the presence of Ca2+ the 2 depolarizing agents release [3H]GABA from the same pool. Pre-exposure to 50mm -K+ in the absence of Ca2+ reduced the second release by 50mm -K+ or by veratridine only by 37 and 27% respectively, indicating that most of the reduction in release was the result of a depletion of releasable [3H]GABA stores. The second exposure to 50mm -K+ in the absence of Ca2+ reduced the evoked release further, while exposure to veratridine in the absence of Ca2+, after depletion of the stores, enhanced release 2.7 times. Electrical stimulation (64 Hz, 2 ms, 40 mA, alternating polarity) during 24min in the presence of Ca” caused an initial 5-fold increase in efflux, which declined subsequently. In the absence of Ca2+, instead of a rapid increase, a slow but smaller increase in the efflux of [3H]GABA was found. TTX almost completely abolished the electrically evoked increase in release. Pre-treatment with 50mm -K+ reduced the electrically evoked release by 94% but electrical stimulation in the absence of Ca2+ after depletion of releasable stores doubled this release. Results suggest that in the presence of Ca2+, high K+, veratridine and electrical stimulation release [3H]GABA from the same Ca2+-dependent store, but in the absence of Ca2+ veratridine and electrical stimulation enhance the release from a Ca2+-independent store, probably as a result of an increased influx of Na+. 相似文献
14.
Exogenous tritiated -aminobutiric acid ([3H]GABA) is retained in two compartments in sheep cortex synaptosomes, corresponding to cytoplasmic and vesicular spaces, assuming that freeze-thawing the synaptosomes loaded with [3H]GABA releases the cytoplasmic [3H]GABA (81±3.9%), and that subsequent solubilization of the synaptosomes with 1% sodium cholate releases the vesicular [3H]GABA (19±3.9%). Depolarization of synaptosomes with 40 mM K+ in a Na+-medium, in the absence of Ca2+, releases 20.3±2.7% of the [3H]GABA retained in the synaptosomes. The [3H]GABA released under these conditions comes predominantly from the cytoplasm. The presence of 1 mM Ca2+ during depolarization releases and additional 13% (a total of about 33.5±9.9%) of the releasable [3H]GABA, and the [3H]GABA release which is Ca2+-dependent also comes mostly from the cytoplasmic compartment. When choline replaces external Na+, the [3H]GABA release is absolutely Ca2+-dependent, and the [3H]GABA released also comes mostly from the cytoplasmic pool. Therefore, it appears that [3H]GABA taken up by synaptosomes is accumulated mostly in the cytoplasmic compartment from which it is released upon depolarization. The technique described permits distinguishing the effect of different factors on the two pools of accumulated [3H]GABA. 相似文献
15.
Mouse cerebral cortical mini-slices were used in a superfusion system to monitor depolarization-induced (55 mM K+) release of preloaded [2,3-3H]GABA and to investigate the biosynthesis of glutamate, GABA and aspartate during physiological and depolarizing (55 mM K+) conditions from either [1,6-13C]glucose or [U-13C]glutamine. Depolarization-induced GABA release could be reduced (50%) by the GABA transport inhibitor tiagabine (25 μM)
or by replacing Ca2+ with Co2+. In the presence of both tiagabine and Co2+ (1 mM), release was abolished completely. The release observed in the presence of 25 μM tiagabine thus represents vesicular
release. Superfusion in the presence of [1,6-13C]glucose led to considerable labeling in the three amino acids, the labeling in glutamate and aspartate being increased after
depolarization. This condition had no effect on GABA labeling. For all three amino acids, the distribution of label in the
different carbon atoms revealed on increased tricarboxylic acid (TCA) activity during depolarization. When [U-13C]glutamine was used as substrate, labeling in glutamate was higher than that in GABA and aspartate and the fraction of glutamate
and aspartate being synthesized by participation of the TCA cycle was increased by depolarization, an effect not seen for
GABA. However, GABA synthesis reflected TCA cycle involvement to a much higher extent than for glutamate and aspartate. The
results show that this preparation of brain tissue with intact cellular networks is well suited to study metabolism and release
of neurotransmitter amino acids under conditions mimicking neural activity.
Special issue article in honor of Dr. Ricardo Tapia. 相似文献
16.
Effect of Nipecotic Acid, a γ-Aminobutyric Acid Transport Inhibitor, on the Turnover and Release of γ-Aminobutyric Acid in Rat Cortical Slices 总被引:11,自引:11,他引:0
John C. Szerb 《Journal of neurochemistry》1982,39(3):850-858
Abstract: To see the effect of a γ-aminobutyric acid GABA uptake inhibitor on the efflux and content of endogenous and labeled GABA, rat cortical slices were first labeled with [3H]GABA and then superfused in the absence or presence of 1 mM nipecotic acid. Endogenous GABA released or remaining in the slices was measured with high performance liquid chromatography, which was also used to separate [3H]GABA from its metabolites. In the presence of 3 mM K+, nipecotic acid released both endogenous and [3H]GABA, with a specific activity four to five times as high as that present in the slices. The release of labeled metabolite(s) of [3H]GABA was also increased by nipecotic acid. The release of endogenous GABA evoked by 50 mM K+ was enhanced fourfold by nipecotic acid but that of [3H]GABA was only doubled when expressed as fractional release. In a medium containing no Ca2+ and 10 mM Mg2+, the release evoked by 50 mMK+ was nearly suppressed in either the absence or the presence of nipecotic acid. In the absence of nipecotic acid electrical stimulation (bursts of 64 Hz) was ineffective in evoking release of either endogenous or [3H]GABA, but in the presence of nipecotic acid it increased the efflux of endogenous GABA threefold, while having much less effect on that of [3H]GABA. Tetrodotoxin (TTX) abolished the effect of electrical stimulation. Both high K+ and electrical stimulation increased the amount of endogenous GABA remaining in the slices, and this increase was reduced by omission of Ca2+ or by TTX. The results suggest that uptake of GABA released through depolarization is of major importance in removing GABA from extracellular spaces, but the enhancement of spontaneous release by nipecotic acid may involve intracellular heteroexchange. Depolarization in the presence of Ca2+ leads to an increased synthesis of GABA, in excess of its release, but the role of this excess GABA remains to be established. 相似文献
17.
Exposure of a crude synaptosomal fraction to K+ concentrations ranging from 25 to 100 mM evokes the release of [3H]taurine and [3H]GABA. These high concentrations of K+ induce, besides depolarization, a marked synaptosomal swelling, which is prevented by replacing chloride in the solutions with the largely impermeant anion gluconate. The depolarizing effect of K+ is unaffected by omission of chloride. The K+-evoked release of taurine seems related to K+-induced changes in synaptosomal volume rather than to a depolarizing effect, since it is totally calcium-independent but is abolished by reducing chloride and by making solutions hypertonic with mannitol. The release of [3H]GABA, in contrast is unaffected in chloride-free or hypertonic solutions. 相似文献
18.
The releases of endogenous glutamate, aspartate, GABA and taurine from hippocampal slices from 7-day-, 3-, 12-, and 18-month-old mice were investigated under cell-damaging conditions using a superfusion system. The slices were superfused under hypoxic conditions in the presence and absence of glucose and exposed to hydrogen peroxide. In the adult hippocampus under normal conditions the basal release of taurine was highest, with a response only about 2-fold to potassium stimulation (50 mM). The low basal releases of glutamate, aspartate, and GABA were markedly potentiated by K+ ions. In general, the release of the four amino acids was enhanced under all above cell-damaging conditions. In hypoxia and ischemia (i.e., hypoxia in the absence of glucose) the release of glutamate, aspartate and GABA increased relatively more than that of taurine, and membrane depolarization by K+ markedly potentiated the release processes. Taurine release was doubled in hypoxia and tripled in ischemia but K+ stimulation was abolished. In both the mature and immature hippocampus the release of glutamate and aspartate was greatly enhanced in the presence of H2O2, that of aspartate particularly in developing mice. In the immature hippocampus the increase in taurine release was 10-fold in hypoxia and 30-fold in ischemia, and potassium stimulation was partly preserved. The release processes of the four amino acids in ischemia were all partially Ca2+-dependent. High concentrations of excitatory amino acids released under cell-damaging conditions are neurotoxic and contribute to neuronal death during ischemia. The substantial amounts of the inhibitory amino acids GABA and taurine released simultaneously may constitute an important protective mechanism against excitatory amino acids in excess, counteracting their harmful effects. In the immature hippocampus in particular, the massive release of taurine under cell-damaging conditions may have a significant function in protecting neural cells and aiding in preserving their viability. 相似文献
19.
GABA is known to be the inhibitory neurotransmitter in the majority of brain stem nuclei. The release of GABA has been extensively
studied both in vivo and in vitro in higher brain areas, whereas the mechanisms of release in the brain stem have not been systemically characterized. The
properties of preloaded [3H]GABA were now investigated in mouse brain stem slices, using a superfusion system. The basal release was enhanced by K+ stimulation (50 mM K+) and under various cell-damaging conditions (ischemia, hypoglycemia, the presence of free radicals and metabolic poisons).
No K+-stimulated release was discernible in the absence of Ca2+, indicating that the release was at least partly Ca2+-dependent. Moreover, the release was increased when Na+ or Cl− was omitted from the superfusion medium. GABA and β-alanine stimulated the release, confirming the involvement of the reversed
function of GABA transporters. Incubation of the slices with the anion channel inhibitors diisothiocyanostilbene and 4-acetamido-4′-isothiocyanostilbene-2,2′-disulphonate
and with the Cl− uptake inhibitor 9-anthracenecarboxylic acid also reduced GABA release, demonstrating that a part of it comprises leakage
through anion channels. All these mechanisms were involved in the ischemia-induced GABA release, which was over 4-fold greater
than the release in normoxia. Contrary to the other brain areas, GABA release in the brain stem was not affected by ionotropic
glutamate receptors but may be modulated by metabotropic receptors. This ischemia-induced GABA release might constitute an
important mechanism against excitotoxicity, protecting the brain stem under cell-damaging conditions.
Special issue dedicated to Dr. Simo S. Oja 相似文献
20.
The influence of tetanus toxin in vitro on the release of exogenous [3H]GABA was studied with rat cerebral cortex slices. The influx, long-term accumulation and spontaneous efflux of GABA were not modified by the toxin. The release induced by high K+ (50 mM) medium from the superfused slices pretreated with the toxin was significantly inhibited in a time- and dose-dependent fashion. This release was attenuated during superfusion with Ca2+-free medium and the toxin no longer affected the remaining Ca2+-independent release. The release induced by Na+-free media did not require extracellular Ca2+ ions, and the toxin inhibited the release both with and without Ca2+. The toxin treatment had no marked influence on the ouabain (20 μM) or veratrine (25–50 μM)-induced release of GABA. The toxin treatment in vitro appears to modify some step(s) in the stimulated release of GABA without affecting its unstimulated membrane transport. Tetanus toxin may thus prove a valuable tool in studying the mechanisms of the release of GABA and possibly other inhibitory transmitters in synapses of the central nervous system. 相似文献