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1.
d-α-Aminoadipate (d-AA) andl-α-aminoadipate (l-AA) were found to significantly reduce spontaneous efflux of [14C]l-aspartate from preloaded rat brain slices. Onlyd-AA significantly reduced spontaneous efflux of [14C]l-glutamate and [3H]γ-aminobutyric acid (GABA);l-AA reduced but not significantly the efflux of these 2 labeled amino acids.d-AA reduced K+-stimulated release of [14C]l-aspartate and [14]C]l-glutamate significantly, andl-AA that of [3H]GABA significantly. Since bothd-AA andl-AA inhibit the uptake ofl-aspartate,l-glutamate and GABA, their effects on the efflux of these amino acids are more specific. These results also suggest that it is unlikely that the depressant effect ofd-AA, and the excitant effect ofl-AA on neurons when applied locally by iontophoresis are secondary to the accelerated or decelerated release of more specific transmitter amino acids from neighboring cells. 相似文献
2.
Inhibition by a recently isolated neurotoxic amino acid, β-N-oxalyl-l-α, β-diaminopropionic acid, (l-BOAA), of stimulated phosphoinositide hydrolysis was studied in rat brain cerebral cortical slices.l-BOAA inhibited the norepinephrine-stimulated response but did not affect hydrolysis induced by 55 mM K+, carbachol in the presence of 20 mM K+. The inhibition was concentration-dependent with anIC50 of 300 μM. This inhibition was insensitive to the excitatory amino acid antagonists, γ-glutamylglycine, glutamic acid diethyl ether, CNQX, AP-4, AP-7, or kynurenate. Thus, we propose that thel-BOAA-mediated inhibition of the norepinephrine-stimulated response was due to an interaction at a novel site, which may also be sensitive to quisqualate (see discussion). The mechanism of the inhibition is still unknown but was not prevented by inhibition of phospholipase A2 or polyamine synthesis and it was not affected by blockade of chloride channels. However, the presence of 20 mM K+ completely blocked the inhibitory effect ofl-BOAA on norepinephrine-stimulated phosphoinositide hydrolysis. 相似文献
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We have investigated the effects of bilateral electrical stimulation of the vagus nerves in anesthetized, paralyzed rats on the release of exogenously administered [3H]l-glutamic acid ([3H]l-Glu) or [3H]d-aspartic acid ([3H]d-Asp) from the intermediate portion of the nucleus tractus solitarius (NTS). Electrical stimulation of afferent fibers with the frequency, pulse, duration, and intensity required to activate C-fibers, elicted hypotension and bradycardia. Such stimuli induced the release of [3H]l-Glu, or its stable analogue [3H]d-Asp, from the NTS into perfusate collected through push-pull cannulae. The release of radioactive materials, calculated as a percent of increase in radioactivity above the prestimulation level, was for [3H]l-Glu 114.4 ± 25.1% (n= 20) during bilateral vagal stimulation, and45.6 ± 11.3% (n= 9) (P < 0.001) during unilateral stimulation. The release of [3H]d-Asp induced by bilateral vagal stimulation was100.4 ± 31.9%. The release, which was anatomically specific and restricted to the NTS, was directly related to stimulus (and hence reflex) intensity. Overflow of the inert substances [14C]urea or [14C]sucrose, co-administered with the [3H]amino acids, did not increase at the same time. Local depolarization of the cells in the NTS by K+ (53 mM) increased the overflow of [3H]l-Glu, as well as [14C]urea, and was able to induce the release of [3H]l-Glu when electrical stimulation failed to have an effect. The results are consistent with the hypothesis thatl-Glu is a neurotransmitter of neurons in the NTS mediating vasodepressor response from vagal afferents, including those from systemic baroreceptors. 相似文献
6.
β-N-Oxalyl-l-α,β-diaminopropionic acid (β-l-ODAP) is an excitatory amino acid agonist found in the seeds ofLathyrus sativus that is believed to be the major causative agent in the pathology of human lathyrism. We have found that in addition to its previously recognized neurotoxic properties, β-l-ODAP is also gliotoxic. When added to cultures of neonatal rat astrocytes, β-l-ODAP induced a series of morphological changes (e.g., extensive vacuole formation, pale and swollen nuclei with obvious nucleoli, and cellular swelling) that led to the eventual lysis of the glial cells. If the β-l-ODAP was removed prior to the lysis of the astrocytes, many of the early morphological changes appeared to be reversible. When quantitated by a loss of the lactate dehydrogenase activity, β-l-ODAP lysed the astrocytes with an LD50 of2.1 ± 0.2mM following 48 h of exposure. Lower concentrations of β-l-ODAP were found to be more toxic if the duration of the exposure was increased. The results suggest that the overall impact of the toxin on the CNS may represent the cumulative action of β-l-ODAP at a number of distinct points on both neurons and astrocytes. The potential that these multiple sites of action may affect the normal regulation of extracellular glutamate and, consequently, disturb the balance between its normal and pathological roles is discussed. 相似文献
7.
The rate of release of [3H]GABA from isolated intact goldfish retinas was studied. Release of [3H]GABA is markedly stimulated by the inclusion in the incubation medium of the photoreceptor neurotransmitter candidates l-glutamate (l-Glu) and l-aspartate (l-Asp), and the glutamate analogs, kainate and quisqualate. At micromolar concentrations, kainate and quisqualate are effective releasers of [3H]GABA, whereas millimolar concentrations of l-Glu and l-Asp are required to release comparable amounts of [3H]GABA. The d-isomers of aspartate (d-Asp) and glutamate (d-Glu) are able to release [3H]GABA, but only when applied at high concentrations (3–30 mM). In the presence of 5 mM d-Asp, the effect of l-Glu in releasing [3H]GABA was markedly potentiated. This dose-response curve of l-Glu was shifted to the left in the presence of d-Asp, although the maximal amount of release was unchanged. d-Asp at 5 mM only slightly increased the GABA release induced by quisqualate, and it did not increase the GABA release induced by kainate. Finally, low concentrations of l-Asp were potentiated by d-Asp, but higher concentrations of l-Asp (3–10 mM) were clearly inhibited by this agent. This biphasic effect of d-Asp on l-Asp-induced release of [3H]GABA is a possible explanation for previously conflicting reports of d-Asp's effect on l-Asp action2,8,29. Our data suggest that d-Asp has both pre- and postsynaptic sites of action. 相似文献
8.
The induction and modification of voltage-sensitive responses in cat neocortical nuerons by N-methyl-d-aspartate 总被引:1,自引:0,他引:1
The actions of the excitatory amino acid, N-methyl-D-aspartate (NMDA), on layer V neurons of cat sensorimotor cortex were examined in an in vitro slice preparation using current clamp, single electrode voltage clamp (SEVC), and ionic substitution techniques. Low doses of NMDA evoked a slow depolarization with a net decrease of input conductance. Larger doses additionally evoked repetitive firing, rhythmic depolarization shifts (DSs), low-threshold calcium spikes (in the presence of TEA+) and bistable membrane potential behavior. Ionic substitution experiments suggested that entry of both Ca2+ and Na+ ions contributed to the NMDA responses. Attention was focused on the NMDA response with Ca2+ entry blocked. Examination by SEVC revealed that, in both normal cells and in the presence of several blocking agents, NMDA induced a highly voltage-dependent inward ionic current which could result in a region of negative slope conductance on the cell's current-voltage relation. The development of this current seems capable of accounting for all aspects of the observed response, including the DSs and low-threshold Ca2+ spikes. Substitution of TEA+ for most external Na+ (with Ca2+ entry blocked) largely eliminated the NMDA responses and corresponding ionic current. Our results in neocortical neurons are compared to those recently obtained in cultured murine neurons. 相似文献
9.
l-Baclofen-sensitive GABAB binding sites in the medial vestibular nucleus (MVN) were identified immunocytochemically and visualized ultrastructurally inl-baclofen-preinjected rats and monkeys, using a mouse monoclonal antibody with specificity for the p-chlorophenyl moiety of baclofen. Saline-preinjected animals showed no immunostain. In drug-injected animals, there was evidence for both pre- and postsynaptic GABAergic inhibition in MVN mediated by GABAB receptors. These neural elements could be utilized in control of velocity storage in the vestibulo-ocular reflex. 相似文献
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The effects of the dicar☐ylic amino acid,dl-α-aminoadipate (DLAA) on amino acid responses have been investigated using intracellular recordings from mouse spinal cord neurons grown in dissociated cell culture.dl-α-Aminoadipate markedly antagonized postsynaptic responses to iontophoretically applied aspartate; antagonism of glutamate was much less prominent.dl-α-Aminoadipate altered the affinity of aspartate for its receptor while having no observed effects on aspartate-receptor cooperativity. No direct effects of DLAA on membrane potentials or passive membrane properties were seen at the currents used for antagonism. Responses to the inhibitory amino acids GABA and glycine were unaffected by DLAA. 相似文献
11.
Slices of mouse cerebellar vermis, cut in the parasagittal plane, were incubated for various times (up to 3 h) in the presence of 1μMd-[3H]aspartate, a non-metabolized substrate for the glutamate/aspartate carrier in brain tissue. Light microscopic autoradiography indicated that in regions away from the cut edges of the slices the amino acid accumulated in glia and granule cells. Relatively few grains were seen over Purkinje, Golgi, stellate and basket cells or over white matter. Grain counts over the granule cell layers in the middle parts of the sliced indicated that after short (15 min) exposures to the labelled substrate, non-granule cell areas (which included glia) contained, on average, slightly more grains than granule cells but wit longer exposures (1.5 and 3 h) the relative grain density over granule cells became much higher, possibly because glial uptake preventsd-[3H]aspartate gaining access to neuronal sites in adequate amounts during short incubations and/or because the longer incubations allow time for retrograde migration of the label from parallel fibre terminals to occur. The demonstration of selective uptake ofd-[3H]aspartate into granule cells contrasts with previous autoradiographic results (possible reasons for which are discussed) and supports the notion thatl-glutamate is the transmitter of granule cells. The results also have a bearing on the importance of the metabolic compartmentation of glutamate in relation to its proposed transmitter role. 相似文献
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Chronic treatment of Sprague-Dawley rats with [d-Ala2,d-Leu5]enkephalin (DADLE) resulted in the development of tolerance to the antinociceptive effect of this opioid peptide. When opioid receptor binding was measured, time-dependent decreases in [3H]diprenorphine binding to the P2 membranes prepared from the cortex, midbrain and striatum were observed. Scatchard analysis of the saturation binding data revealed a decrease in Bmax values and no change in the Kd values of [3H]diprenorphine binding to these brain regions, indicative of down-regulation of the receptor. This reduction in the opioid receptor binding activities could be demonstrated to be due to the DADLE effect on the δ-opioid receptors in these brain regions. When [3H]DADLE binding was carried out in the presence of morphiceptin, a significant reduction in the δ-opioid receptor binding was observed in all brain areas tested. μ-Opioid receptor binding decrease was observed only in the striatum after 5 days of DADLE treatment. Additionally, the onset of δ-opioid receptor decrease in the midbrain area was rapid, within 6 h of the initiation of the chronic DADLE treatment. Thus, analogous to previous observations in which chronic etorphine treatment preferentially reduced μ-opioid receptor binding, chronic DADLE treatment preferentially reduced δ-opioid receptor binding activity. 相似文献
13.
The γ-aminobutyric acid (GABA) synthesizing enzyme,l-glutamate decarboxylase (GAD), and the taurine synthesizing enzyme, cysteinesulfinic acid decarboxylase (CSAD) have been localized in rat retina at the ultrastructural level by indirect immunoelectron microscopy. GAD immunoreactivity (GAD-IR) was seen only in some amacrine cells and their terminals. CSAD immunoreactivity (CSAD-IR) was found in most retinal neuronal types and their processes including photoreceptor cells (rod and cone cells), bipolar cells, amacrine cells and ganglion cells. The GAD-IR positive amacrine terminals have been found to make synaptic contact with other GAD-IR negative bipolar and amacrine terminals, and ganglion cell dendrites. Most of the GAD-IR positive terminals are presynaptic. Occasionally, GAD-IR positive amacrine terminals are postsynaptic to another amacrine terminal or ganglion cell body. In the inner plexiform layer, CSAD-IR positive amacrine terminals also make synaptic contacts with other nerve terminals, similar to that of GAD-IR positive amacrine terminals. In addition, CSAD-IR positive bipolar terminals make synaptic contact with some CSAD-IR positive as well as negative amacrine terminals. Both CSAD-IR positive amacrine and bipolar terminals are mostly presynaptic to other CSAD-IR negative terminals. In the outer plexiform layer, CSAD-IR was found to be associated with synaptic vesicles and the synaptic membrane in certain cone pedicles and rod spherules. It is concluded that only a fraction of amacrine cells in rat retina may use GABA as a neurotransmitter. The presence of CSAD-IR in some amacrine, bipolar, photoreceptor and ganglion cells in rat retina is compatible with the notion that taurine may play some important roles, such as those of neurotransmitter or neuromodulator in mammalian retina. 相似文献
14.
Three compounds reportedly blocking the N-methyl-d-aspartate (NMDA) receptor, namely 2-amino-5-phosphonovalerate, γ-d-glutamylglycine and 3-hydroxy-2-quinoxalinecar☐ylic acid, were injected subdurally onto the cortex of freely moving rats. All 3 compounds effectively suppressed behavioral and electrographic seizure activity induced by strychnine, morphine and picrotoxin that were administered via the same route. The cortical application of the NMDA-receptor antagonists did not induce behavioral or electrographic changes, and behavioral side-effects commonly observed following intracerebroventricular administration of these compounds were absent. The anatomical separation of anticonvulsant action and side-effects induced by these compounds suggests that this class of compounds may eventually be useful as antiepileptic drugs. 相似文献
15.
M. Kimura K. Shikada H. Nojima I. Kimura 《International journal of developmental neuroscience》1986,4(1):61-67
The effects of alpha-bungarotoxin (alpha-BuTX), D-tubocurarine (D-TC) and antibodies against muscle extract on acetylcholine (ACh) sensitivity were investigated in developing mouse myotubes in a nerve-muscle co-culture. Antibodies clearly suppressed the ACh potential amplitude in adult mouse diaphragm muscle, but antibodies in muscle pre-treated with D-TC (1 microgram/ml) weakly suppressed it. The addition of D-TC to muscle extract dose-dependently inhibited the formation of the immunoprecipitation lines. The exposure of developing myotubes to antibodies for 10 days in culture suppressed both resting potential and ACh potential, whereas co-existence of alpha-BuTX (1 microgram/ml) or D-TC (0.1 mg/ml) with antibodies suppressed ACh potential but did not affect resting potential compared with antibodies alone. The ACh potentials in myotubes cultured with alpha-BuTX and D-TC alone were also suppressed. The appearance (day 8 in culture) of this suppressive effect by alpha-BuTX was faster than that (day 11 in culture) of D-TC. These different effects depending on the time in culture may account for the conformational change of developing ACh receptors to alpha-BuTX and D-TC. 相似文献
16.
The anatomical distribution ofl-[3H]glutamate binding sites was determined in the presence of various glutamate analogues using quantitative autoradiography. The binding ofl-[3H]glutamate is accounted for the presence of 3 distinct binding sites when measured in the absence of Ca2+, Cl− and Na+ ions. The anatomical distribution and pharmacological specificity of these binding sites correspond to that reported for the 3 excitatory amino acid binding sites selectively labeled byd-[3H]2-amino-5-phosphonopentanoate (d-[3H]AP5), [3H]kainate ([3H]KA) and [3H]α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid ([3H]AMPA) which are thought to be selective ligands for the N-methyl-d-aspartate (NMDA), KA and quisqualate (QA) receptors, respectively. 相似文献
17.
Anticonvulsant action of β-kainic acid in mice. Is β-kainic acid an N-methyl-d-aspartate antagonist? 总被引:1,自引:0,他引:1
An effect of the beta-stereoisomer of kainic acid on seizures produced by intracerebroventricular injections of excitatory amino acids was tested in mice. beta-Kainic acid preferentially antagonizes myoclonic seizures induced by N-methyl-D-aspartate and quinolinate, has less pronounced anticonvulsant action against alpha-kainate, D-homocysteinesulphinate and quisqualate, and no effect on convulsions induced by L-glutamate. The anticonvulsant activity of beta-kainic acid matches that of 2-amino-7-phosphonoheptanoic and kynurenic acids, both preferential N-methyl-D-aspartate receptor antagonists, and differs considerably from the profile of anticonvulsant action of gamma-D-glutamylaminomethylsulphonic acid, a preferential kainate/quisqualate antagonist. 相似文献
18.
Differential pulse voltammetry used together with electrochemically pretreated carbon fibre microelectrodes allowed us to detect in vivo two well-separated peaks in nucleus accumbens and olfactory tubercle. The two peaks situated at −50 mV (peak 1) and +100 mV (peak 2) correspond, respectively, to the oxidation current of the ascorbic acid and to the oxidation current of the 3,4-dihydroxyphenylacetic acid (DOPAC). The experiments were carried out on anesthetized rats. Voltammograms were recorded in nucleus accumbens and olfactory tubercle every minute alternately in each structure. In control conditions, peak 1 height was greater in olfactory tubercle than in nucleus accumbens and peak 2 height was greater in nucleus accumbens than in olfactory tubercle. Both isomers of amphetamine induced a decrease of the peak 2 height in the two structures. The decrease was greater in olfactory tubercle. Higher doses of l-amphetamine were required to induce peak 2 height decrease of the same extent. Both isomers induced a marked increase of the peak 1 height in nucleus accumbens whereas peak 1 height in olfactory tubercle was slightly augmented. d-amphetamine was more effective than l-amphetamine in increasing peak 1 height. 相似文献
19.
Intracellular and extracellular recordings from CA3 hippocampal neurons in vitro were used to study the ability of several NMDA (N-methyl-d-aspartate) receptor antagonists to suppress epileptiform bursts induced by NMDA and convulsants not thought to act at NMDA receptors. The antagonists, APV (d-2-amino-5-phosphonovalerate), AP-7 (d,l-2-amino-7-phosphonoheptanoate) and CPP (d,l-3-[(±)-2-car☐ypiperazin-4-yl-]-propyl-1-phosphonic acid), blocked the spontaneous and evoked bursts induced by NMDA. CPP, but not APV or AP-7, prevented the development of bursts induced by Mg-free medium. The NMDA antagonists failed to block bursting induced by kainate, 7 mM K+, mast cell degranulating peptide, anoxia or spontaneous bursting. In some cases the NMDA antagonists induced spontaneous bursts or enhanced burst frequency, a proconvulsant effect. It is concluded that activation of NMDA receptors is sufficient but not necessary for burst generation in the CA3 region. 相似文献
20.
Using antisera against tyrosine hydroxylase (TH) and aromatic l-amino acid decar☐ylase (AADC), we have demonstrated the presence of numerous AADC immunoreactive neurons and few TH immunoreactive neurons, Homogeneously distributed throughout the suprachiasmatic nucleus. Similar results have been described in other species. These observations show that this nucleus is able to synthesize trace amines (such as phenylethylamine or tyramine) in addition to dopamine. It is hypothesized that these trace amines are possibly involved in the integration of day length variation in sheep, a species whose reproduction is closely related to photoperiod. 相似文献