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1.
谷氨酸NMDA受体与惊厥 总被引:6,自引:0,他引:6
本文介绍了近几年对谷氨酸NMDA受体的研究进展,并就中枢神经系统中,NMDA受体发育,分布特点及其受体激动剂与拮挤在惊厥中的作用等方面探讨了该受体与惊厥产生,发展和扩散的关系,同时也概述了惊厥发生机制中NMDA受体可能起的作用。 相似文献
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谷氨酸下调培养海马神经元AMPA受体G1uR2亚单位的表达 总被引:1,自引:0,他引:1
目的 研究在癫痫发病过程中,谷氨酸对AMPA受体G1uR2亚单位表达变化的影响。方法 用RT-PCR和Western Blot方法观察谷氨酸诱导培养大鼠海马神经元AMPA受体G1uR2亚单位mRNA和蛋白的表达变化。结果 在谷氨酸刺激后2h,8h,12h,培养海马神经元G1uR2 mRNA和蛋白表达明显下降,与对照组相比,差异有显著性(P〈0.05),而非NMDA受体拮抗剂CNQX能阻断此变化。结论 在癫痫等疾病中,谷氨酸能通过激活AMAP/KA受体下调AMPA受体G1uR2亚单位的表达,参与发病过程。 相似文献
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本工作在酶解分离的鲫鱼视网膜水平细胞上研究了AMPA受体对γ-氨基丁酸(γ-aminobutyric acid,GABA)转运体电流的调节作用。由1mmol/L GABA所诱导的GABA转运体电流被持续50s的AMPA(30μmol/L或3mmol/L)预灌流所抑制。在细胞内液中施加10mmol/L BAPTA可以减弱AMPA对GABA转运体电流的抑制效应。施加3mmol/L AMPA+3mmol/ LNMDA所引起的抑制效应和单独施加3mmol/L AMPA或3mmol/L NMDA所引起的抑制效应相仿。以上结果表明,和激活NMDA受体调节GABA转运体的机制一样,激活视网膜水平细胞上的AMPA受体可以通过胞内钙过程来抑制GABA转运体电流。 相似文献
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目的:研究丁苯酞(NBP)对酒精依赖大鼠海马谷氨酸(Glu)含量和NNMDA受体2B亚基(NR2B)表达的影响。方法:建立酒精成瘾大鼠模型,观察戒断症状,SYBR Green I荧光实时定量PCR技术检测海马区NR2BmRNA表达,高效液相色谱法检测海马组织中谷氨酸含量。结果:模型组大鼠戒断评分比正常组明显上升(P<0.01),NBP中、高剂量组与模型组相比,戒断评分明显下降(P<0.05),差异均有显著性;模型组大鼠海马区谷氨酸含量较正常组显著降低(P<0.01),差异有显著性,而各用药组与模型组相比,海马区谷氨酸含量差异无显著性(P>0.05);实时定量PCR结果表明模型组大鼠海马区NR2BmRNA表达较正常组明显增加(P<0.05),而NBP中、高剂量组与模型组相比,海马区NR2BmRNA表达明显减少,差异有显著性(P<0.05)。结论:NBP能够减轻酒精依赖大鼠的戒断症状,可能与NBP抑制NR2BmRNA表达有关。 相似文献
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药物成瘾及成瘾记忆的研究现状 总被引:17,自引:0,他引:17
本文在介绍药物成瘾与学习和记忆密切相关的神经回路及共同分子机制的基础上,围绕学习和记忆在药物成瘾中的作用,综述了关联性学习与复吸,关联性学习与敏化,异常关联性学习与强迫性用药行为,关联性学习及成瘾记忆与成瘾,多重记忆系统与成瘾的发生发展等方面的研究进展,并强调了突触可塑性及成瘾记忆在药物成瘾中的重要性。在此基础上提出:作为慢性脑病的药物成瘾的形成过程的重要特征是它包含着信息的特殊学习类型。药物成瘾与依赖于多巴胺的关联性学习紊乱有密切关系。海马可能在成瘾中扮演重要角色。 相似文献
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本文用免疫组织化学ABC法调查了4种AMPA受体亚单位(GluR1、2/3、4)和谷氨酸(Glu)在大鼠三叉神经尾侧亚核(Vc)内的分布及其匹配关系。我们发现,GluR1和2/3免疫阳性胞体和纤维密集分布于Vc的Ⅱ层和Ⅲ层外侧部,在Vc的其余各层呈散在性分布。GluR4免疫阳性胞体和纤维在Vc各层均无分布。Glu免疫阳性胞体分布于Vc各层,尤以浅层(Ⅰ、Ⅱ层)密集,Glu免疫阳性纤维及终末结构主要分布于Vc浅层。结果表明,Glu免疫阳性纤维及终末样结构与AMPA受体免疫阳性胞体和纤维在Vc浅层的分布总体上是相互匹配的,但AMPA受体各亚单位在Vc内的分布存在明显的差异。本文提示,Vc内的Glu可能通过作用于不同的AMPA受体亚单位而发挥其多种生理功能 相似文献
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Rubio ME 《Molecular neurobiology》2000,21(1-2):1-19
Glutamate receptors mediate the majority of excitatory responses in the central nervous system (CNS). Neurons express multiple
subtypes and subunits of glutamate receptors, which are differentially distributed at pre- and postsynaptic sites. This allows
the cell to respond differentially depending on the subunit composition of receptors at the postsynaptic membrane. The process
by which receptors are targeted selectively to the appropriate synapse is poorly understood. Evidence exists that targeting
of glutamate receptors to the different neuronal compartments is regulated at multiple levels involving a general targeting
step; a local step where receptor-containing organelles are moved to the synapse; and a step where the receptors are stabilized
at the synapse, which may involve interaction with an anchoring protein. 相似文献
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Ossowska K Pietraszek M Wardas J Nowak G Zajaczkowski W Wolfarth S Pilc A 《Amino acids》2000,19(1):87-94
Summary. It has recently been postulated that disturbances in glutamatergic neurotransmission may contribute to the pathophysiology
of schizophrenia. Therefore the aim of the present study was to evaluate the role of glutamate NMDA and group II metabotropic
receptors in the antipsychotic drug action. To this aim the influence of some well-known neuroleptics on cortical NMDA receptors
was examined. Furthermore, their behavioral effects were compared with those of the novel agonist of group II glutamate metabotropic
receptors, LY 354740, in some animal models of schizophrenic deficits. We found that long-term administration of the typical
neuroleptic haloperidol and the atypical one clozapine increased the number of NMDA receptors labelled with [3H]CGP 39653 in different cortical areas. Long-, but not short-term, treatment with haloperidol and raclopride diminished the
deficit of prepulse inhibition produced by phencyclidine, which is a model of sensorimotor gating deficit in schizophrenia.
In contrast, neither short- nor long-term treatment with clozapine influenced the phencyclidine effect in that model. Acute
treatment with LY 354740 reversed neither (1) the deficit of prepulse inhibition produced by phencyclidine or apomorphine,
nor (2) the impairment in a delayed alternation task induced by MK-801, which is commonly used to model the frontal lobe deficits
associated with schizophrenia. The present study suggests that an increase in the density of cortical NMDA receptors may be
important to a longterm neuroleptic therapy. Conversely, the results do not support the role of group II metabotropic glutamate
receptors in the antipsychotic drug action.
Received August 31, 1999 Accepted September 20, 1999 相似文献
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Denis B. Tikhonov 《Molecular membrane biology》2013,30(2):135-147
Ionotropic glutamate receptors belong to the superfamily of P-loop channels as well as K+, Na+, and Ca2+ channels. However, the structural similarity between ion channels of the glutamate receptors and K+ channels is a matter of discussion. The aim of this study was to analyze differences between the structures of K+ channels and glutamate receptor channels. For this purpose, homology models of NMDA and AMPA receptor channels (M2 and M3 segments) were built using X-ray structures of K+ channels as templates. The models were optimized and used to reproduce specific data on the structure of glutamate receptor channels. Particular attention was paid to the data of the binding of channel blockers and to the results of scanning mutagenesis. The modeling demonstrates that properties of glutamate receptor channel can be reproduced assuming only local structural deformations of the K+ channel templates. The most valuable differences were found in the selectivity-filter region, whereas helical parts of M2 and M3 segments could have similar spatial organization with homologous segments in K+ channels. It is concluded that the current experimental data on glutamate receptor channels does not reveal global structural differences with K+ channels. 相似文献
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The mechanism of presynaptic long-term depression mediated by group I metabotropic glutamate receptors 总被引:2,自引:0,他引:2
1. Metabotropic glutamate receptors (mGluRs) are known to play a role in synaptic plasticity. In a study of rat hippocampal brain slices, we find that a brief perfusion of a group I mGluR agonist, (S)-3,5-dihydroxyphenylglycine (DHPG), induced a robust long-term depression (DHPG-LTD) in area CA1.2. The action was accompanied by an enhancement of the paired-pulse facilitation (PPF) ratio.3. At the same time DHPG enhanced ionophoretic responses to alpha-amino-3- hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA), kainic acid (KA), and N-methyl-D-aspartate (NMDA) in CA1 pyramidal neurons. This was only partially reversed by washing.4. These observations indicate that DHPG exerts two opposing actions, suppression of the synaptic transmission and facilitation of postsynaptic responses. However, the presynaptic action dominates, since the net effect of monosynaptic activation is a reduction of response.5. Perfusion of DHPG reduced three calcium-dependent responses in CA3 pyramidal neurons, which are presynaptic to CA1 neurons. These are calcium spike width and amplitude, after-hyperpolarization (AHP), and spike frequency adaptation (SFA).6. These results suggest that the DHPG-LTD results from modulation of the presynaptic calcium currents by group l mGluRs. 相似文献
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Christine Peterson Maryse Héroux Joel Lavoie Dr. Roger F. Butterworth 《Neurochemical research》1995,20(10):1155-1160
Previous studies suggest that alterations of brain glutamate synthesis and release occur in experimental thiamine deficiency. In order to assess the integrity of post-synaptic glutamatergic receptors in thiamine deficiency, binding sites for [3H]glutamate (displaced by NMDA), [3H]-kainate, and [3H]quisqualate (AMPA sites) were evaluated using Quantitative Receptor Autoradiography in rat brain following 14 days of treatment with the central thiamine antagonist pyrithiamine. Compared to pair-fed controls, brains of symptomatic thiamine-deficient animals contained significantly fewer NMDA-displaceable binding sites in cerebral cortex, medial septum and hippocampus. It has been suggested that NMDA-receptor mediated glutamate excitotoxicity plays a role in the pathogenesis of neuronal loss in thiamine deficiency. If such is the case, the selective loss of NMDA binding sites in cerebral cortex and hippocampus offers a possible explanation for the relative nonvulnerability of these brain regions to pyrithiamine-induced thiamine deficiency. [3H]quisqualate (AMPA) binding sites were unchanged in all brain regions of pyrithiamine-treated rats whereas [3H]kainate sites were significantly reduced in density in medial and lateral thalamus. The decline in these binding sites may be due to neuronal loss in pyrithiamine-induced thiamine deficiency. Alterations of glutamatergic synaptic function involving both NMDA and kainate receptor subclasses could contribute to the pathogenesis of neurological dysfunction in Wernicke's Encephalopathy in humans. 相似文献
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Novel approaches to targeting glutamate receptors for the treatment of chronic pain: review article 总被引:2,自引:0,他引:2
Chizh BA 《Amino acids》2002,23(1-3):169-176
Summary. Glutamatergic mechanisms are implicated in acute and chronic pain, and there is a great diversity of glutamate receptors
that can be used as targets for novel analgesics. Some approaches, e.g. NMDA receptor antagonism, have been validated clinically,
however, the central side-effects have remained the main problem with most compounds. Recently, some novel approaches have
been explored as new compounds targeting some modulatory sites at the NMDA receptor (glycineB and NR2B-subtype selective antagonists), as well as kainate and metabotropic glutamate receptors, have been discovered. Many
of these compounds have demonstrated efficacy in animal models of chronic pain, and some of them appear to have a reduced
side-effect liability compared to clinically tested NMDA antagonists. These recent advances are reviewed in the present work.
Received July 6, 2001 Accepted August 6, 2001 Published online June 26, 2002 相似文献
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A detailed pharmacological characterization of metabotropic glutamate receptors (mGluR) was performed in primary cultures of cerebellar granule cells at 6 days in vitro (DIV). The rank order of agonists induced polyphosphoinositide (PPI) hydrolysis (after correcting for the ionotropic component in the response) was as follows: in terms of efficiency, Glu>quisqualate (quis)=ibotenate (ibo)>(1S,3R)-1-amino-cyclopentane-1,3-dicarboxylic acid (ACPD)>-methyl-amino-l-alanine (BMAA) and in terms of potency, quis>ACPD>Glu>ibo=BMAA. Ionotropic excitatory amino acid (EAA) receptor agonists, such as -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) were relatively inactive (in the presence of Mg2+). Quis and ACPD-induced PPI hydrolysis was unaffected by ionotropic Glu receptor antagonists, but was inhibited, in part by L-2-amino-3-phosphonopropionate (AP3). In contrast, Glu-or ibo- induced PPI hydrolysis was reduced, in part, by both AP3 and NMDA receptor antagonists. Characteristic interactions involving different transmitter receptors were noted. PPI hydrolysis evoked by quis and 1S,3R-ACPD was not additive. In contrast, PPI hydrolysis stimulated by quis/ACPD and carbamylcholine was additive (indicating different receptors/transduction pathways). In the presence of Mg2+, the metabotropic response to quis/AMPA and NMDA was synergistic (this being consistent with AMPA receptor-induced depolarization activating NMDA receptor). On the other hand, in Mg2+-free buffer the effects of quis and NMDA, at concentrations causing maximal PPI hydrolysis, were additive (indicating that PPI hydrolysis was effected by two different mechanisms). Thus, in cerebellar granule cells EAAs elicit PPI hydrolysis by acting at two distinct receptor types: (i) metabotropic Glu receptors (mGluR), with pharmacological characteristics suggesting the expression of a unique mGluR receptor that shows certain similarities to those observed for the mGluR1 subtype (Aramori and Nakanishi, 1992) and (ii) NMDA receptors. The physiological agonist, Glu, is able to stimulate both receptor classes.Abbreviations ACPD
(1S,3R)-1-amino-cyclopentane-1,3-dicarboxylic acid
- AMPA
-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid
- AP3
L-2-amino-3-phosphono-propionate
- AP5
D-2-amino-5-phosphonopentenoate
- BMAA
-methyl-amino-L-alanine
- DIV
days in vitro
- DNOX
6,7-dinitroouinoxoline-2,3-dione
- EAA
excitatory amino acids
- Glu
glutamate
- InsP
inositol monophosphate
- mGluR
metabotropic glutamate receptors
- MK-801
(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]-cyclohept-5,10-imine hydrogen maleate
- NMDA
N-methyl-D-aspartate
- PPI
polyphosphoinositide
- quis
quisqualate 相似文献
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T. R. Soderling S. E. Tan E. McGlade-McCulloh H. Yamamoto K. Fukunaga 《Developmental neurobiology》1994,25(3):304-311
One of the most active areas of neurobiology research concerns mechanisms involved in paradigms of synaptic plasticity. A popular model for cellular leaning and memory is long term potentiation (LTP) in hippocamus. LTP requires postsynaptic influx of Ca2+ which triggers multiple biochemical pathways resulting in pre- and postsynaptic mechanisms enhancing long term synaptic efficiency. This article focuses on an acute postsynaptic Mechanism that can enhance responsiveness of glutamate receptors. Evidence is presented that calcium/calmodulin/dependent protein kinase II, the major potsynaptic density protein at excitatory glutaminergic synapses, can phosphorylate glutamate receptors and enhance ion current flowing through them. 1994 John Wiley & Sons, Inc. 相似文献
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Circadian rhythms generated by the hypothalamic suprachiasmatic nucleus (SCN) are synchronized with the external light/dark cycle by photic information transmitted directly from the retina via the retinohypothalamic tract (RHT). The RHT contains the neurotransmitters glutamate and pituitary adenylate cyclase-activating polypeptide (PACAP), which code chemically for 'light' or 'darkness' information, respectively. We investigated interactions of PACAP and glutamate by analysing effects on the second messenger calcium in individual SCN neurons using the Fura-2 technique. PACAP did not affect NMDA-mediated calcium increases, but influenced signalling cascades of non-NMDA glutamate receptors, which in turn can regulate NMDA receptors. On the one hand, PACAP amplified/induced glutamate-dependent calcium increases by interacting with alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate signalling. This was not related to direct PACAPergic effects on the second messengers cAMP and calcium. On the other hand, PACAP reduced/inhibited calcium increases elicited by glutamate acting on metabotropic receptors. cAMP analogues mimicked this inhibition. Most neurons displaying PACAPergic neuromodulation were immunoreactive for vasoactive intestinal polypeptide, which is a marker for retinorecipient SCN neurons. The observed PACAPergic effects provide a broad range of interactions that allow a fine-tuning of the endogenous clock by the integration of 'light' and 'darkness' information on the level of single SCN neurons. 相似文献