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1.
Purified synaptic vesicles were isolated from hog cerebral cortex by a rapid procedure consisting of homogenization of cerebral cortex slices in iso-osmotic sucrose, differential centrifugation and sucrose density-gradient centrifugation. The purity of the vesicles was evaluated both biochemically and morphologically. The vesicles contained high amounts of γ-aminobutyrate (GABA) and acetylcholine at specific concentrations of 390 nmol/mg protein and 7.2 nmol/mg protein respectively. Glutamate decarboxylase, the enzyme which catalyses GABA formation, binds to the synaptic vesicles in a calcium-dependent manner. The percentage of glutamate decarboxylase bound to the vesicles increases from about 5% without calcium, reaching a plateau of about 60% at 4 mM Ca2+. Magnesium in concentrations 0.2–10 mM has no significant effect on glutamate decarboxylase binding. Also in phospholipid vesicles (small unilamellar phosphatidylserine-phosphatidylcholine. 2:1 liposomes) Ca2+, but not Mg2+, induced the binding of glutamate decarboxylase, reaching a plateau of 50% at 2 mM Ca2+. Both in synaptic vesicles and in phospholipid vesicles the calcium-dependent glutamate decarboxylase binding seems to be specific, and not caused by unspecific association of proteins, since the specific binding (bound enzyme activity/mg bound protein) increases 3-fold from 0 to 4 mM Ca2+. The functional role of this binding was studied in GAD containing vesicles by measuring the relationship between the accumulation of [3H]GABA, newly synthetized from [3H]glutamate, and the uptake of added [14C]GABA. No significant uptake of [14C]GABA was found under the experimental conditions used, whereas large amounts of [3H]GABA were found within the vesicles. It appears that the [3H]GABA accumulation process is functionally linked to [3H]GABA synthesis and is mediated by the membrane-bound glutamate decarboxylase. This synthesis-coupled uptake of GABA into synaptic vesicles possibly serves to bring about a plasticity effect in previously stimulated GABAergic nerve endings. 相似文献
2.
Fluoxetine, a selective 5-HT uptake inhibitor, inhibited 15 mM K +-induced [ 3H] 5-HT release from rat spinal cord and cortical synaptosomes at concentrations > 0.5 uM. This effect reflected a property shared by another selective 5-HT uptake inhibitor paroxetine but not by less selective uptake inhibitors such as amitriptyline, desipramine, imipramine or nortriptyline. Inhibition of release by fluoxetine was inversely related to both the concentration of K + used to depolarize the synaptosomes and the concentration of external Ca 2+. Experiments aimed at determining a mechanism of action revealed that fluoxetine did not inhibit voltage-independent release of [ 3H] 5-HT release induced by the Ca 2+-ionophore A 23187 or Ca 2+-independent release induced by fenfluramine. Moreover the 5-HT autoreceptor antagonist methiothepin did not reverse the inhibitory actions of fluoxetine on K +-induced release. Further studies examined the effects of fluoxetine on voltage-dependent Ca 2+ channels and Ca 2+ entry. Whereas fluoxetine and paroxetine inhibited binding of [ 3H] nitrendipine to the dihydropyridine-sensitive L-type Ca 2+ channel, the less selective uptake inhibitors did not alter binding. The dihydropyridine antagonist nimodipine partially blocked fluoxetine-induced inhibition of release. Moreover enhanced K +-stimulated release due to the dihydropyridine agonist Bay K 8644 was reversed by fluoxetine. Fluoxetine also inhibited the K +-induced increase in intracellular free Ca 2+ in fura-2 loaded synaptosomes. These data are consistent with the suggestion that fluoxetine inhibits K +-induced [ 3H] 5-HT release by antagonizing voltage-dependent Ca 2+ entry into nerve terminals. 相似文献
3.
Rabbit retinac preloaded with [ 3H]adenosine were superfused in vitro and the effect of neurotransmitter agonists and antagonists on the release of [ 3H]purines was studied. Glutamic acid, aspartic acid, kainic acid (KA), quisqualic acid (QUIS) and
acid (NMDA) all stimulated the efflux of [ 3H] labelled and endogenous purines. Their effect was reduced in a Ca 2+-free medium except when using a high concentration (100 μM) of KA, QUIS and NMDA. The effect of aspartic acid and of NMDA were blocked by 2-amino-7-phosphono-heptanoic acid (APH) and 2-amino-5-phosphono-valeric acid (APV). Carbachol also increased the release of adenosine-derived radioactivity and this effect was reduced by the removal of Ca 2+ and by pretreatment with atropine. τ-Aminobutyric acid (GABA) and muscimol, induced a small increase in the release which was Ca 2+-dependent and was blocked by bicuculline and picrotoxin. Dopamine elicited an increase in the release which was partially reduced in a Ca 2+-free medium and was blocked by haloperidol. Glycine and 5-hydroxytryptamine (5-HT) also induced small but significant increases. The neurotransmitter antagonists had an effect of their own. Superfusion with APH and APV depressed the outflow of radioactivity whereas bicuculline, picrotoxin, strychnine and haloperidol enhanced it. The K +-evoked release of [ 3H]purines was reduced by haloperidol and by 5-HT. The observations indicate that stimulation of several important neurotransmitter receptors in the retina elicits the release of adenosine derivatives. The results with the antagonists also suggest that purines are continuously released as a result of a tonic activation of the respective membrane receptors. 相似文献
4.
Ontogenetic development and Ca 2+-dependence of the K +-stimulated release of [ 3H]γ-aminobutyric acid (GABA) were studied by two different methods using tissue slices in vitro. The results indicate that, in the developing rat cortex, the K +-stimulated release of [ 3H]GABA is initially very low but it develops rapidly during the second and third postnatal weeks. This supports an earlier study which concluded that, during the cortical ontogeny, the ratio of stimulated: resting release of [ 3H]GABA increased at the fastest rate about 9–12 days after the birth, thus preceding the formation of GABAergic synapses by about 10 days. Furthermore, most of the early postnatal release observed in the present experiments is Ca 2+-independent. An important Ca 2+-dependent component of the release appears at later developmental stages and it also seems to develop faster than the GABAergic synapses. The present study suggests that the stimulus-coupled release of GABA in the rat cortex profoundly changes during the ontogeny, both quantitatively (the period of rapid development) and qualitatively (with respect to Ca 2+-dependence). These observations, possibly reflecting changes in the association of GABA release with different structures (e.g. initially axonal growth cones, then neuronal dendrites and only at later stages GABAergic synapses) may be important in the evaluation of the putative role of GABA in synaptogenesis. 相似文献
5.
Release of [ 3H]dopamine ([ 3H]DA) from rat striatal slices kept under hypoxic or/and glucose-free conditions was measured using a microvolume perfusion method. The corresponding changes in nucleotide content were determined by reverse-phase high-performance liquid chromatography (RPHPLC). The resting release of [ 3H]DA was not affected by hypoxia, but under glucose-free conditions massive [Ca 2+] 0-independent release of [ 3H]DA was observed. Hypoxia reduced the energy charge (E.C.) and the total purine content from 19.36 ± 4.15 to 6.98 ± 1.83 mol/mg protein. Glucose deprivation by itself, or in combination with hypoxia, markedly reduced the levels of adenosine 5′-triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate (AMP). The E.C. under glucose-free conditions was significantly reduced from 0.73 ± 0.04 to 0.44 ± 0.20. When the tissue was exposed to hypoxic and glucose-free conditions for 18 min the level of ATP was reduced to 3.15 ± 0.11 mol/mg protein. However, when the exposure time was 30 min the ATP level was further reduced to 1.11 ± 0.37 nmol/mg protein. The resting release was enhanced in a [Ca 2+] 0-independent manner, but there was no release in response to stimulation, and tetrodotoxin did not affect the enhanced resting release, indicating that the release was not associated with axonal activity. Similarly, 50 μM ouabain, inhibitor of Na +/K +-activated ATPase, enhanced the release of [ 3H]DA at rest in a [Ca 2+] 0-independent manner. It seems very likely that the reduced ATP level under glucose-free conditions leads to an inhibition of the activity of Na +/K +-ATPase that results in reversal of the uptake processes and in [Ca 2+] 0-independent [ 3H]DA release from the axon terminals. 相似文献
6.
Glutamate transiently stimulated rat pheochromocytoma PC12 cells and caused an inositol trisphosphate formation and an increase in levels of Ca + in the cytosol. The rank order of potency of glutamate> N-methyl-D-aspartate (NMDA) > KAINATE = quisqualate is characteristic of an interaction with NMDA receptors. The effect of glutamate on inositol trisphosphate formation disappeared in a low Mg 2+ buffer and was not blocked by DL-2-amino-5-phosphonovalerate, an antagonist for NMDA receptors coupled to ion channels. Although glutamate failed to stimulate noradrenaline secretion, glutamate enhanced the effect of bradykinin, but not of Ca ionophore A23187, or KC1. These results suggest the existence of metabotropic glutamate receptors, different from previously reported receptors, in PC12 cells. 相似文献
7.
In order to examine intracellular modulation of CNS catecholamine release, cerebrocortical synaptosomes were prelabeled with [ 3H]noradrenaline and permeabilized with streptolysin-O in the absence or presence of Ca 2+. Plasma membrane permeabilization allowed efflux of cytosol and left a compartmentalized pool of [ 3H]noradrenaline intact, approximately 10% of which was released by addition of 10 −5 M Ca 2+. Addition of activators or inhibitors of protein kinase C, as well as inhibitors of Ca 2+-calmodulin kinase II or calcineurin, failed to change Ca 2+-induced noradrenaline release. Evoked release from permeabilized synaptosomes deficient in the vesicle-associated phosphoprotein synapsin I was also unchanged. In contrast, addition of a synthetic ‘active domain’ peptide from the myristoylated, alanine-rich C-kinase substrate (MARCKS) protein increased, while addition of calmodulin decreased Ca 2+-induced release from the permeabilized synaptosomes, the latter effect being reversed by a peptide inhibitor of calcineurin. Moreover, addition of the actin-destabilizing agent DNase I, as well as antibodies to MARCKS, appeared to increase spontaneous, Ca 2+-independent release from noradrenergic vesicles. These results indicate that the MARCKS protein may modulate release from permeabilized noradrenergic synaptosomes, possibly by modulating calmodulin levels and/or the actin cytoskeleton. 相似文献
8.
Abstract: In vivo microdialysis was used in conjunction with a novel dual-label preloading method to monitor changes in extracellular levels of γ-aminobutyric acid (GABA) and glutamate due to N -methyl- d -aspartate (NMDA) infusion in the striatum of conscious, unrestrained rats. [ 14C]GABA and [ 3H]glutamate were applied in the dialysis stream for a preloading period of 30 min, after which dialysis perfusion was continued for up to 6 h and dialysate samples were collected for analysis by liquid scintillation spectrometry. NMDA (300 μ M in the dialysate) caused significant rises in both 14C and 3H content measured in the dialysates, the majority of which remained associated with the preloaded GABA and glutamate, respectively. The NMDA-evoked release of both GABA and glutamate was blocked by the specific NMDA receptor antagonist 3-[(±)-2-carboxypiperazin-4-yl]propyl-1-phosphonic acid (CPP), indicating that the response was receptor mediated. The NMDA-stimulated release of glutamate was also totally abolished by concomitant application of the adenosine agonist 2-chloroadenosine or by prior frontal decortication. However, these two treatments caused little change in NMDA-evoked GABA release. These results show that NMDA causes release of GABA from the striatum in vivo by an NMDA receptor-mediated mechanism and that the majority of this release is not secondary to glutamate release from terminals of the corticostriate pathway. In addition, they confirm the results of previous studies investigating the effect of NMDA on endogenous glutamate release. 相似文献
9.
Phospholipase A 2 added directly to superfused [ 3H]norepinephrine-labeled synaptosomes could cause the release of neurotransmitter molecules. Chloroquine and quinacrine, which block the action of phospholipase A 2, inhibited either the phospholipase A 2-stimulated or the high potassium-stimulated release of [ 3H]norepinephrine from synaptosomes. Only quinacrine blocked the high potassium-stimulated influx of Ca 2+. It appears that during stimulation of synaptosomes, Ca 2+ influx leads to the activation of phospholipase A 2, which in turn, hydrolyzes membrane phospholipids in situ. The formation of lysophospholipids may alter the microenvironment and the physicochemical properties of membranes, resulting in the release of neurotransmitter through exocytosis. 相似文献
10.
Abstract: In primary cultures of cerebellar granule cells, glutamate, aspartate, and N -methyl-d-aspartate (NMDA) induced a dose-dependent release of [ 3H]arachidonic acid ([ 3H]AA) which was selective for these agonists and was inhibited by NMDA receptor antagonists. The agonist-induced [ 3H]AA release was reduced by quinacrine at concentrations that inhibited phospholipase A 2 (PLA 2) but affected neither the activity of phospholipase C (PLC) nor the hydrolysis of phosphoinositides induced by glutamate or quisqualate. Thus, the increased formation of AA was due to the receptor-mediated activation of PLA 2 rather than to the action of PLC followed by diacylglycerol lipase. The receptor-mediated [ 3H]AA release was dependent on the presence of extracellular Ca 2+ and was mimicked by the Ca 2+ ionophore ionomycin. Pretreatment of granule cells with either pertussis or cholera toxin failed to inhibit the receptor-mediated [ 3H]AA release. Hence, in cerebellar granule cells, the stimulation of NMDA-sensitive glutamate receptors leads to the activation of PLA 2 that is mediated by Ca 2+ ions entering through the cationic channels functioning as effectors of NMDA receptors. A coupling through a toxin-sensitive GTP-binding protein can be excluded. 相似文献
11.
Abstract: The mechanism of glutamate release from cultured cerebellar granule neurones in response to a chemical model of ischaemia (10 m M 2-deoxyglucose plus 1 m M sodium cyanide) was investigated. In the first 2 min of ischaemia, release of preloaded d -[ 3H]aspartate could be extensively attenuated by tetanus toxin and bafilomycin A 1 and was dependent on the activation of Ca 2+ channels sensitive to the "Q" type Ca 2+ channel antagonist, ω-conotoxin-MVIIC. During this period, ATP/ADP ratios fell rapidly. The extent of release in the first 2 min was comparable to that evoked by 2-min depolarization by 50 m M KCl. Free Ca 2+ concentrations, determined in neurites and somata, did not increase until after 2 min. The neurite increase in cellular Ca 2+ precedes that of the cell somata. Release of d -[ 3H]aspartate was partially inhibited by the NMDA receptor antagonist MK-801, which also delayed the increase in free Ca 2+ concentration. Prolonging the period of ischaemia to 6 and 10 min produced no further increase in the apparently exocytotic component of release, but initiated an extensive nonexocytotic release of the amino acid. Studies with the synaptic vesicle membrane probe FM1-43 in which released amino acid was removed by superfusion indicated that Ca 2+-dependent exocytosis was delayed in this system. It is concluded that chemical ischaemia initiates an initial exocytotic followed by nonexocytotic release and that the former is facilitated by NMDA receptor activation. These events occur in cells that are still able to exclude propidium iodide, indicating that cell death has not yet occurred. 相似文献
12.
Release of γ-aminobutyric acid (GABA) can be elicited by electrical field stimulation even in the absence of external Ca 2+. Indeed, the release of GABA under such conditions is even higher than in the presence of Ca 2+. To investigate the underlying mechanism of this phenomenon, the release of endogenous GABA from rat striatal slices was measured by high performance liquid chromatography with electro- chemical detection. Electrical stimulation at 2 Hz for 3 min elevated GABA efflux by 4.5-fold. Withdrawing external Ca 2+ and adding 1 mM EGTA produced a small, transient increase in the basal efflux of GABA and increased electrically-evoked overflow 3-fold. Tetrodotoxin (5 μM) did not affect basal efflux in either normal or Ca 2+-free conditions, but abolished electrically-evoked release. In the presence of normal Ca 2+, nipecotic acid (1 mM) enhanced both spontaneous efflux and evoked overflow. Nipecotic acid also increased spontaneous release when external Ca 2+ was removed. However, in the absence of Ca 2+, nipecotic acid failed to increase electrically evoked GABA overflow. These results suggest that there exists a Ca 2+-independent process for GABA release via the same carrier system that is utilized for high affinity GABA uptake. 相似文献
13.
In the superior cervical ganglion (SCG) of rats, the interaction of sodium bromide (NaBr) with various drugs which interfere with the GABA system, such as 3-(4-chlorophenyl)-4-aminobutyrate [( + )baclofen, Bac], ( + )bicuculline (Bic), picrotoxin (Pic) and chlorpromazine (CPZ), and the effects of NaBr on the K +-induced release of [ 3H]acetylcholine ([ 3H]ACh) were studied in vitro. The effects on the evoked potentials induced by preganglionic stimulation were analysed in situ. The in vitro experiments revealed that 1 mM NaBr inhibits both the basal and the K +-induced release of [ 3H]ACh in a Ca 2+-dependent manner. This NaBr effect was additive with the similar effect of the GABA agonist Bac, but it could not be blocked with any of the drugs applied. In vivo, 1 mM NaBr depressed the amplitude of the evoked potentials in the SCG. It is concluded that, in the SCG of rats, NaBr interacts with the presynaptic and postsynaptic membranes. The inhibitory effects of NaBr on both the [ 3H]ACh release and the potentials evoked by preganglionic stimulation cannot be attributed to a direct interference with GABA receptor complexes; some other binding site/s on the presynaptic and postsynaptic membranes might be responsible for the bromide-induced reduction of the synaptic transmission in the SCG of rats. 相似文献
14.
The effects of excitatory amino acids and some analogues on the release of GABA and ACh from amacrine cells were studied. The release of endogenous GABA from the isolated rat retina was measured by HPLC. When animals were pretreated with γ-vinyl-GABA (GVG), glutamate evoked a large efflux of GABA but kainate, quisqualate and
( NMDA) were relatively ineffective. The glutamate evoked release of GABA was calcium dependent and was blocked by the antagonist, piperidine-dicarboxylic acid (PDA) indicating that activation of excitatory amino acid receptors was involved in the response. The release of [ 3H]ACh from the rabbit retina was strikingly increased by homocysteate and this effect was blocked by NMDA. Since NMDA also blocked the light evoked release of [ 3H]ACh but not the effects of exogenous glutamate or aspartate, it is possible that homocysteate may be a bipolar cell transmitter released onto cholinergic amacrine cells. 相似文献
15.
Abstract: We demonstrated that glutamate increased the cyclic AMP level in cultured neurons from rat spinal cord. A bath application of glutamate (300 µ M ) elicited a rapid increase of the cyclic AMP concentration reaching a level three times as high as the basal level in ∼3 min, and its content then decreased to the control level in 15 min. The increase was not observed in a Ca 2+-free medium and was inhibited by an antagonist of NMDA receptors or a voltage-sensitive Ca 2+ channel blocker. Preincubation with W7 also inhibited the glutamate-evoked cyclic AMP increase. NMDA, aspartate, and high-K + conditions also induced a cyclic AMP increase; however, a decreasing phase did not follow. The decreasing phase was observed when (2 S ,1' S ,2' S )-2-(carboxycyclopropyl)-glycine, a potent agonist for metabotropic glutamate receptors, was combined with NMDA. These results suggest that the cyclic AMP increase is mediated by a Ca 2+ influx via both NMDA receptors and voltage-sensitive Ca 2+ channels followed by an activation of the Ca 2+/calmodulin system, and the decreasing phase observed in the case of glutamate exposure is due to the activation of the metabotropic glutamate receptors. 相似文献
16.
Abstract: For the purpose of demonstrating the action of taurine as a neuromodulator in addition to its suggested neurotransmitter function, the effects of taurine and muscimol on the depolarization-induced Ca-dependent release of [ 3H]γ-aminobutyric acid (pH]GABA) and l -[ 3H]glutamate in cerebellar slices from guinea pigs were investigated. The release of [ 3H]GABA was found to be greatly decreased by a GABA agonist, muscimol, and by taurine, but not by glycine. The release of l -[ 3H]glutamate was little affected by taurine. The release of [ 3H]GABA was enhanced by bicuculline and strychnine, but not by picrotoxin, and the suppressive action of muscimol on the GABA release was antagonized by bicuculline, picrotoxin, and strychnine, suggesting the possible existence of presynaptic autoreceptors for GABA in the cerebellum. The suppressive action of taurine on the release of [ 3H]GABA, on the other hand, was blocked only by bicuculline. These results suggest that taurine reduced the release of [ 3H]GABA from cerebellar slices by acting on the GABA autoreceptors or, more likely, on other types of receptors that are sensitive to bicuculline. As a possible mechanism for this modulatory action of taurine, the blockade by this amino acid of the influx of Ca 2+ into cerebellar tissues was tentatively suggested. 相似文献
18.
Extracellular ATP dose dependently stimulated 45Ca 2+ influx even in the presence of nifedipine, a Ca 2+ antagonist that inhibits voltage-dependent Ca 2+ channel, in osteoblast-like MC3T3-E1 cells. ATP stimulated arachidonic acid release and the synthesis of prostaglandin E 2 (PGE 2). However, the ATP-induced arachidonic acid release was significantly reduced by chelating extracellular Ca 2+ with EGTA. On the other hand, ATP induced DNA synthesis of these cells in a dose-dependent manner in the range between 1μM and 1 mM. The pretreatment with indomethacin, a cyclooxygenase inhibitor, suppressed both ATP-induced PGE 2 synthesis and DNA synthesis in these cells. The inhibitory effect by 50μM indomethacin on the DNA synthesis was reversed by adding 10μM PGE 2. These results strongly suggest that extracellular ATP stimulates Ca 2+ influx resulting in the release of arachidonic acid in osteoblast-like cells and that extracellular ATP-induced proliferative effect is mediated, at least in part, by ATP-stimulated PGE 2 synthesis. 相似文献
19.
Glutathione (γ-glutamylcysteinylglycine, GSH and oxidized glutathione, GSSG), may function as a neuromodulator at the glutamate
receptors and as a neurotransmitter at its own receptors. We studied now the effects of GSH, GSSG, glutathione derivatives
and thiol redox agents on the spontaneous, K +- and glutamate-agonist-evoked releases of [ 3H]dopamine from mouse striatal slices. The release evoked by 25 mM K + was inhibited by GSH, S-ethyl-, -propyl-, -butyl- and pentylglutathione and glutathione sulfonate. 5,5′-Dithio-bis-2-nitrobenzoate (DTNB) and l-cystine were also inhibitory, while dithiothreitol (DTT) and l-cysteine enhanced the K +-evoked release. Ten min preperfusion with 50 μM ZnCl 2 enhanced the basal unstimulated release but prevented the activation of K +-evoked release by DTT.
Kainate and 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) evoked dopamine release but the other glutamate receptor
agonists N-methyl- d-aspartate (NMDA), glycine (1 mM) and trans-1-aminocyclopentane-1,3-dicarboxylate (t-ACPD, 0.5 mM), and the modulators GSH, GSSG, glutathione sulfonate, S-alkyl-derivatives of glutathione, DTNB, cystine, cysteine and DTT (all 1 mM) were without effect. The release evoked by 1 mM
glutamate was enhanced by 1 mM GSH, while GSSG, glutathionesulfonate and S-alkyl derivatives of glutathione were generally without effect or inhibitory. NMDA (1 mM) evoked release only in the presence
of 1 mM GSH but not with GSSG, other peptides or thiol modulators. l-Cysteine (1 mM) enhanced the glutamate-evoked release similarly to GSH. The activation by 1 mM kainate was inhibited by S-ethyl-, -propyl-, and -butylglutathione and the activation by 0.5 mM AMPA was inhibited by S-ethylglutathione but enhanced by GSSG.
Glutathione alone does not directly evoke dopamine release but may inhibit the depolarization-evoked release by preventing
the toxic effects of high glutamate, and by modulating the cysteine–cystine redox state in Ca 2+ channels. GSH also seems to enhance the glutamate-agonist-evoked release via both non-NMDA and NMDA receptors. In this action,
the γ-glutamyl and cysteinyl moieties of glutathione are involved. 相似文献
20.
Rat brain cortex slices preincubated with [ 3H]serotonin or [ 3H]noradrenaline (25 100 nmol/l each) were superfused and the effects of serotonin and histamine on the electrically (0.3 or 3 Hz) evoked tritium overflow were studied. In slices preincubated with [3H]serotonin the extent of inhibition of the electrically (3 Hz) evoked tritium overflow produced by histamine was increased when the concentration of [3H]serotonin used for incubation was decreased. The evoked overflow tended to be lower in slices from 2-year-old rats than in slices from 6-month-old animals whereas the inhibitory effect of histamine on the evoked overflow did not differ. Treatment of rats with nimodipine for at least 6 weeks did not significantly affect the evoked overflow in slices from 6-month and 2-year-old rats nor did it significantly alter the serotonin- and histamine-mediated inhibition of the evoked overflow in slices from young adult rats. The extent of histamine-mediated inhibition of the electrically evoked tritium overflow from slices (of young adult rats) preincubated with [3H]noradrenaline did not change when the concentration of [3H]noradrenaline used for incubation was decreased; the degree of inhibition markedly increased when the frequency of stimulation was lowered from 3 to 0.3 Hz. The inhibitory effect of histamine on the electrically (0.3 Hz) evoked overflow was mimicked by the H3 receptor agonist R-(−)--methylhistamine and antagonized by the H3 receptor antagonist thioperamide. The electrically evoked overflow and its inhibition by histamine were not affected by nimodipine, irrespective of whether the Ca2+ antagonist was administered in vivo (for at least 6 weeks) or added to the superfusion medium in vitro. It is concluded that (1) the extent of the H3 receptor-mediated effect in rat brain cortex slices can be markedly increased by lowering the concentration of the tracer in slices preincubated with [3H]serotonin and by lowering the stimulation frequency in slices preincubated with [3H]noradrenaline; (2) the H3 receptor-mediated inhibition of serotonin release is not changed during aging and (3) nimodipine does not significantly influence serotonin release and noradrenaline release and their serotonin and/or histamine receptor-mediated modulation. 相似文献
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