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1.
The vertebrate retina is a “genuine neural center” (Ramón y Cajal), in which glutamate is a major excitatory neurotransmitter.
Both N-methyl-d-aspartate (NMDA) and non-NMDA receptors are expressed in the retina. Although non-NMDA receptors and/or metabotropic glutamate
receptors are generally thought to be responsible for mediating the transfer of visual signals in the outer retina, there
is recent evidence suggesting that NMDA receptors are also expressed in photoreceptors, as well as horizontal and bipolar
cells. In the inner retina, NMDA receptors, in addition to other glutamate receptor subtypes, are abundantly expressed to
mediate visual signal transmission from bipolar cells to amacrine and ganglion cells, and could be involved in modulation
of inhibitory feedback from amacrine cells to bipolar cells. NMDA receptors are extrasynaptically expressed in ganglion cells
(and probably amacrine cells) and may play physiological roles in a special mode. Activity of NMDA receptors may be modulated
by neuromodulators, such as d-serine and others. This article discusses retinal excitotoxicity mediated by NMDA receptors. 相似文献
2.
In addition to their role in orchestrating body and tentacle contractions, hydra’s nerves control the behavior of nematocysts;
precisely how is still a work in progress. There are strong indications that the classical neurotransmitters, glutamate and
GABA (γ-amino-butyric acid), play an essential role in effecting stenotele and desmoneme discharge. In experiments on isolated
tentacles of Hydra vulgaris, in which cnidocils were mechanically deflected with a piezo-electrically-driven glass micropipette, stenoteles and desmonemes
respond to differences in applied force in a dose-dependent manner. GABA, working through its metabotropic receptor, appears
to be involved with the recruitment of desmonemes. Desmonemes in distant battery cells or in another part of a given battery
cell were discharged by stimulating a desmoneme cnidocil in the presence of bath-applied GABA or its metabotropic agonist,
baclofen. The effect was blocked by phaclofen, its metabotropic antagonist. Neither GABA nor baclofen affected stenotele discharge.
GABAA agonists had no effect on nematocyst discharge. Glutamate caused a significant increase in number of stenoteles responding
to direct mechanical stimuli, but did not effect desmoneme discharge. The effect was mimicked by NMDA (n-methyl-d-aspartate) together with kainate, or by NMDA plus AMPA (amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid), but not with
any ionotropic agonist alone. The effect was blocked by D-AP 5 (d- (−)–2-amino–5-phosphopentanoic acid), a specific NMDA antagonist, or CNQX (6-cyano-7-nitroquinoxaline-2,3-dione), a specific
kainate/AMPA antagonist. A glutamatergic mechanism working through ionotropic glutamate receptors appears to lower the firing
threshold of stenoteles, perhaps␣by permitting the entry of Ca2+ into the cell through the early evolved NMDA/kainite/AMPA mechanism. 相似文献
3.
N-methyl-D-aspartate (NMDA) receptors play a crucial role in Glutamate (l-Glu) neurotoxicity. To evaluate the effects of astrocyte-derived tryptophan metabolite kynurenic acid (KYNA), on l-Glu neurotoxicity, adult male rats were pretreated with Kynurenine (KYN) which is a precursor of KYNA, at a dose of 30 mg
or 300 mg/kg bw i.p., 2 h before stereotactic l-Glu bolus (1μmole/1 μl) administration in cerebral cortex. Results showed that acute l-Glu increased reactive oxygen species, rate of lipid peroxidation, calcium, nitric oxide and neuroinflammatory markers viz.
TNF-α, IFN-γ levels and decreased key antioxidant parameters such as SOD, catalase, total glutathione and glutathione reductase
along with mitochondrial membrane potential. While peripheral loading of 30 mg/kg dose of KYN had no protective effects on
l-Glu induced neurotoxicity, 300 mg/kg dose prevented the above toxic effects following intracortical l-Glu. KYN apparently crossed blood brain barrier to elevate astrocytic-KYNA level, which seems to protect neurons through
several interactive mechanisms. 相似文献
4.
Benneyworth MA Li Y Basu AC Bolshakov VY Coyle JT 《Cellular and molecular neurobiology》2012,32(4):613-624
d-Serine, which is synthesized by the enzyme serine racemase (SR), is a co-agonist at the N-methyl-d-aspartate receptor (NMDAR). Crucial to an understanding of the signaling functions of d-serine is defining the sites responsible for its synthesis and release. In order to quantify the contributions of astrocytes
and neurons to SR and d-serine localization, we used recombinant DNA techniques to effect cell type selective suppression of SR expression in astrocytes
(aSRCKO) and in forebrain glutamatergic neurons (nSRCKO). The majority of SR is expressed in neurons: SR expression was reduced by ~65% in nSRCKO cerebral cortex and hippocampus, but only ~15% in aSRCKO as quantified by western blots. In contrast, nSRCKO is associated with only modest decreases in d-serine levels as quantified by HPLC, whereas d-serine levels were unaffected in aSRCKO mice. Liver expression of SR was increased by 35% in the nSRCKO, suggesting a role for peripheral SR in the maintenance of brain d-serine. Electrophysiologic studies of long-term potentiation (LTP) at the Schaffer collateral–CA1 pyramidal neuron synapse
revealed no alterations in the aSRCKO mice versus wild-type. LTP induced by a single tetanic stimulus was reduced by nearly 70% in the nSRCKO mice. Furthermore, the mini-excitatory post-synaptic currents mediated by NMDA receptors but not by AMPA receptors were
significantly reduced in nSRCKO mice. Our findings indicate that in forebrain, where d-serine appears to be the endogenous co-agonist at NMDA receptors, SR is predominantly expressed in glutamatergic neurons,
and co-release of glutamate and d-serine is required for optimal activation of post-synaptic NMDA receptors. 相似文献
5.
A comparative study was done using J774A.1 and J774A. 1-derived transfected cells (J774A.1 C.1) containing antisense tumor
necrosis factor α (TNF-α) plasmid to determine the role of endogenous TNF-α on nitric oxide production as well as on the growth
ofMycobacterium microti in interferon γ (IFN-γ)- and lipopolysaccharide (LPS)-treated cells. On stimulation with IFN-γ and LPS a higher level of
NO was observed in J774A.1 cells compared to J774A.1 C.1 which indicated that endogenous TNF-α is required for the production
of NO. Comparing the effect of IFN-γ and LPS on the intracellular growth ofM. microti, the growth-reducing activity was higher in J774A.1 cells than in J774A.1 C.1 cells and was not completely abrogated in the
presence of the nitric oxide inhibitorN
G-methyl-l-arginine (l-NMA). J774A.1 C.1 cells infected withM. microti produced a significant amount of NO when exogenous TNF-α was added along with IFN-γ and LPS and the concentration of intracellular
bacteria decreased almost to that in IFN-γ and LPS treated parental J774A.1 cells. Addition of exogenous TNF-α even in the
presence ofl-NMA in J774.1 C.1 cells could also partially restore intracellular growth inhibition ofM. microti caused by IFN-γ and LPS. TNF-α is probably required for the production of NO in J774A.1 cells by IFN-γ and LPS but TNF-α
and NO are independently involved in the killing of intracellularM. microti with IFN-γ and LPS. 相似文献
6.
Evidence that brain glutamatergic activity is pathologically elevated in bipolar disorder suggests that mood stabilizers are
therapeutic in the disease in part by downregulating glutamatergic activity. Such activity can involve the second messenger,
arachidonic acid (AA, 20:4n − 6). We tested this hypothesis with regard to valproic acid (VPA), when stimulating glutamatergic N-methyl-d-aspartate (NMDA) receptors in rat brain and measuring AA and related responses. An acute subconvulsant dose of NMDA (25 mg/kg
i.p.) or saline was administered to unanesthetized rats that had been treated i.p. daily with VPA (200 mg/kg) or vehicle for
30 days. Quantitative autoradiography following intravenous [1-14C]AA infusion was used to image regional brain AA incorporation coefficients k*, markers of AA signaling. In chronic vehicle-pretreated
rats, NMDA compared with saline significantly increased k* in 41 of 82 examined brain regions, many of which have high NMDA
receptor densities, and also increased brain concentrations of the AA metabolites, prostaglandin E2 (PGE2) and thromboxane B2 (TXB2). VPA pretreatment reduced baseline concentrations of PGE2 and TXB2, and blocked the NMDA induced increases in k* and in eicosanoid concentrations. These results, taken with evidence that carbamazepine
and lithium also block k* responses to NMDA in rat brain, suggest that mood stabilizers act in bipolar disorder in part by
downregulating glutamatergic signaling involving AA. 相似文献
7.
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 ZnCl2 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 Ca2+ 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
8.
Intraperitoneal injection of 1 mg/kg reserpine into rats caused the development of behavioral depression that was especially
clearly pronounced 24 h after injection. Under such conditions, induction of long-term potentiation of synaptic transmission
was suppressed, the development of long-term depression in glutamatergic synapses of pyramidal neurons of the hippocampal
CA1 area and layers II/III of the parietal cortex was facilitated, and metaplasticity threshold (θM) was shifted to the right. Such modifications of plasticity and metaplasticity of glutamatergic synapses were determined
by changes in the functional state of postsynaptic NMDA receptors, which was confirmed by a decrease in the duration of NMDA
component of field EPSPs generated in the studied neurons and by an increase in the sensitivity of this component to the action
of a nonselective blocker of NMDA receptors, ketamine. Simultaneously, the sensitivity to zinc and haloperidol, which are
selective with respect to NMDA receptors with the subunit composition NR1/NR2B, decreased. It is hypothesized that, under
conditions of depression, either replacement of a part of NR2B subunits in the structure of NMDA receptors by NR2A subunits
or biochemical inactivation of NMDA receptors containing NR2B subunit, as well as a decrease in the clearance of transmitter
in glutamatergic synapses, occur; these events determine the impairment of plastic properties of the latter contacts.
Neirofiziologiya/Neurophysiology, Vol. 39, No. 3, pp. 214–221, May–June, 2007. 相似文献
9.
A growing body of evidence indicates that neuronal nicotinic acetylcholine receptors (nAChRs), in addition to promoting fast
cholinergic transmission, may modulate other neuronal activities within the central nervous system (CNS). In particular, the
α7 nAChR is highly permeable to Ca2+ and may serve a distinct role in regulating neuronal plasticity. By elevating intracellular Ca2+ levels in discrete neuronal locations, these ligand-gated ion channels may influence numerous physiological processes in
developing and adult CNS. In this article, we review evidence that both pre- and postsynaptic α7 nAChRs modulate transmitter
release in the brain and periphery through Ca2+-dependent mechanisms. The possible role of α7 nAChRs in regulating neuronal growth and differentiation in developing CNS
is also evaluated. We consider an interaction between cholinergic and glutamatergic transmission and propose a hypothesis
on the possible coregulation of intracellular Ca2+ byN-methyl-d-aspartate (NMDA) receptors and α7 nAChRs. Finally, the clinical significance of alterations in the normal function of α7
nAChRs is discussed as it pertains to prenatal nicotine exposure, schizophrenia, and epilepsy. 相似文献
10.
Function of GABAergic and glutamatergic neurons in the stomach 总被引:1,自引:1,他引:0
Tsai LH 《Journal of biomedical science》2005,12(2):255-266
-Aminobutyric acid (GABA) and L-glutamic acid (L-Glu) are transmitters of GABAergic and glutamatergic neurons in the enteric interneurons, targeting excitatory or inhibitory GABA receptors or glutamate receptors that modulate gastric motility and mucosal function. GABAergic and glutamatergic neuron immunoreactivity have been found in cholinergic enteric neurons in the stomach. GABA and L-Glu may also subserve hormonal and paracrine signaling. Disruption in gastrointestinal function following perturbation of enteric GABA receptors and glutamate receptors presents potential new target sites for drug development. 相似文献
11.
Glutamate is the main excitatory neurotransmitter of the central nervous system (CNS), released both from neurons and glial cells. Acting via ionotropic (NMDA, AMPA, kainate) and metabotropic glutamate receptors, it is critically involved in essential regulatory functions. Disturbances of glutamatergic neurotransmission can be detected in cognitive and neurodegenerative disorders. This paper summarizes the present knowledge on the modulation of glutamate-mediated responses in the CNS. Emphasis will be put on NMDA receptor channels, which are essential executive and integrative elements of the glutamatergic system. This receptor is crucial for proper functioning of neuronal circuits; its hypofunction or overactivation can result in neuronal disturbances and neurotoxicity. Somewhat surprisingly, NMDA receptors are not widely targeted by pharmacotherapy in clinics; their robust activation or inhibition seems to be desirable only in exceptional cases. However, their fine-tuning might provide a promising manipulation to optimize the activity of the glutamatergic system and to restore proper CNS function. This orchestration utilizes several neuromodulators. Besides the classical ones such as dopamine, novel candidates emerged in the last two decades. The purinergic system is a promising possibility to optimize the activity of the glutamatergic system. It exerts not only direct and indirect influences on NMDA receptors but, by modulating glutamatergic transmission, also plays an important role in glia-neuron communication. These purinergic functions will be illustrated mostly by depicting the modulatory role of the purinergic system on glutamatergic transmission in the prefrontal cortex, a CNS area important for attention, memory and learning. 相似文献
12.
Ambrish J. Patel Anthony Hunt Wendy Jacques-Berg Jozsef Kiss Jose Rodriguez 《Neurochemical research》1995,20(5):561-569
The role of protein kinase C (PKC) in N-methyl-d-aspartate (NMDA) receptor-mediated biochemical differentiation and c-fos protein expression was investigated in cultured cerebellar granule neurons. The biochemical differentiation of glutamatergic granule cells was studied in terms of the specific activity of phosphate-activated glutaminase, an enzyme important in the synthesis of the putative neurotransmitter pool of glutamate. When the partially depolarized cells were treated with NMDA for the last 1 to 3 days (between 2 and 5 days in vitro), it elevated the specific activity of glutaminase. In contrast, NMDA had little effect on the activity of aspartate aminotransferase or of lactate dehydrogenase. Treatment of 10-day old granule neurons with NMDA also resulted in a marked increase in the immunocytochemically measured expression of c-fos protein. The increases in both the activity of glutaminase and the steady state level of c-fos protein were specific to the activation of NMDA receptors, as they were completely blocked byd,l-2-amino-5-phosphonovaleric acid. The specific stimulation of NMDA receptors in PKC-depleted granule neurons or in the presence of reasonably specific PKC inhibitors also produced significant elevation in the activity of glutaminase and the expression of c-fos protein. These increases were similar in magnitude to those observed in the granule neurons of the respective control groups. Our findings demonstrate that PKC is not directly involved in the NMDA receptor-mediated signal transduction processes associated with biochemical differentiation and c-fos induction in cerebellar granule neurons. 相似文献
13.
Nagy Katalin Marko Bernadett Zsilla Gabriella Matyus Peter Pallagi Katalin Szabo Geza Juranyi Zsolt Barkoczy Jozsef Levay Gyorgy Harsing Laszlo G. 《Neurochemical research》2010,35(12):2096-2106
The most dominant hypotheses for the pathogenesis of schizophrenia have focused primarily upon hyperfunctional dopaminergic
and hypofunctional glutamatergic neurotransmission in the central nervous system. The therapeutic efficacy of all atypical
antipsychotics is explained in part by antagonism of the dopaminergic neurotransmission, mainly by blockade of D2 dopamine receptors. N-methyl-d-aspartate (NMDA) receptor hypofunction in schizophrenia can be reversed by glycine transporter type-1 (GlyT-1) inhibitors,
which regulate glycine concentrations at the vicinity of NMDA receptors. Combined drug administration with D2 dopamine receptor blockade and activation of hypofunctional NMDA receptors may be needed for a more effective treatment of
positive and negative symptoms and the accompanied cognitive deficit in schizophrenia. To investigate this type of combined
drug administration, rats were treated with the atypical antipsychotic risperidone together with the GlyT-1 inhibitor Org-24461.
Brain microdialysis was applied in the striatum of conscious rats and determinations of extracellular dopamine, DOPAC, HVA,
glycine, glutamate, and serine concentrations were carried out using HPLC/electrochemistry. Risperidone increased extracellular
concentrations of dopamine but failed to influence those of glycine or glutamate measured in microdialysis samples. Org-24461
injection reduced extracellular dopamine concentrations and elevated extracellular glycine levels but the concentrations of
serine and glutamate were not changed. When risperidone and Org-24461 were added in combination, a decrease in extracellular
dopamine concentrations was accompanied with sustained elevation of extracellular glycine levels. Interestingly, the extracellular
concentrations of glutamate were also enhanced. Our data indicate that coadministration of an antipsychotic with a GlyT-1
inhibitor may normalize hypofunctional NMDA receptor-mediated glutamatergic neurotransmission with reduced dopaminergic side
effects characteristic for antipsychotic medication. 相似文献
14.
l-Glutamic acid (l-Glu) and other excitatory amino acids and amino acid analogs enhanced [35S]thiocyanate (SCN–) uptake in isolated-resealed synaptic membrane vesicles. The SCN– uptake was used as a measure of membrane depolarization to evaluate the characteristics of functional excitatory amino acid receptors in the synaptic membranes.N-Methyl-d-aspartate (NMDA) andl-Glu produced additive effects on SCN– accumulation indicating the presence of distinctl-Glu and NMDA receptors. On the other hand, kainic acid (KA) andl-Glu shared either common receptor sites or ion channels. The effects of antagonists on NMDA,l-Glu, and KA stimulation of SCN– influx were consistent with previously reported electrophysiologic observations in intact neurons. 相似文献
15.
Ion channels: molecular targets of neuroactive insecticides 总被引:2,自引:0,他引:2
Raymond-Delpech V Matsuda K Sattelle BM Rauh JJ Sattelle DB 《Invertebrate neuroscience : IN》2005,5(3-4):119-133
Many of the insecticides in current use act on molecular targets in the insect nervous system. Recently, our understanding of these targets has improved as a result of the complete sequencing of an insect genome, i.e., Drosophila melanogaster. Here we examine the recent work, drawing on genetics, genomics and physiology, which has provided evidence that specific receptors and ion channels are targeted by distinct chemical classes of insect control agents. The examples discussed include, sodium channels (pyrethroids, p,p′-dichlorodiphenyl-trichloroethane (DDT), dihydropyrazoles and oxadiazines); nicotinic acetylcholine receptors (cartap, spinosad, imidacloprid and related nitromethylenes/nitroguanidines); γ-aminobutyric acid (GABA) receptors (cyclodienes, γ-BHC and fipronil) and L-glutamate receptors (avermectins). Finally, we have examined the molecular basis of resistance to these molecules, which in some cases involves mutations in the molecular target, and we also consider the future impact of molecular genetic technologies in our understanding of the actions of neuroactive insecticides. 相似文献
16.
Recombinant human interferon-gamma (rhIFN-γ) is a protein of great potential for clinical therapy due to its multiple biological
activities. However, overexpressing rhIFN-γ in Escherichia coli was found to accumulate as cytoplasmic inclusion bodies. In this work, a system for soluble and active expression of rhIFN-γ
was constructed by coexpressing chaperonin GroEL/GroES in E. coli. The rhIFN-γ gene was fused to a pET-28a expression vector, and rhIFN-γ was partially expressed as the soluble form following
coexpression with a second vector producing chaperonin GroEL/GroES. The fermentation of recombinant E. coli harboring rhIFN-γ and GroEL/GroES plasmids was investigated, and the optimized conditions were as follows: culture temperature
of 25°C, incubation time of 8 h, isopropyl-β-d-thio-galactoside concentration of 0.2 mM, and l-arabinose concentration of 0.5 g/L. As a result, the expression level of rhIFN-γ was improved accordingly by 2.2-fold than
the control, while a significantly positive correlation was also found between the ratio of supernatant to precipitate of
rhIFN-γ and the amount of chaperonin. Circular dichroism spectra, fluorescence spectra, size exclusion chromatography, and
chemical cross-linking method were applied to characterize rhIFN-γ, indicating that the three-dimensional structure of rhIFN-γ
was identical to that of the native rhIFN-γ. The enzyme-linked immunosorbent assay for active rhIFN-γ quantification showed
that coexpression yielded 72.91 mg rhIFN-γ per liter fermentation broth. Finally, protein–protein interactions between rhIFN-γ
and chaperonin were analyzed using the yeast two-hybrid system, which provided the direct evidence that chaperonin GroEL/GroES
interacted with rhIFN-γ to increase the soluble expression and presented the potential in producing efficiently recombinant
proteins. 相似文献
17.
Receptors for excitatory amino acid,L-glutamate, have been classified into three subtypes named as N-methyl-D-aspartate (NMDA), quisqualate (QA) and kainate receptors. In the present study, an effect of age on binding sites of [3H]-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (3H-AMPA), a QA agonist, was studied in the rat brain through quantitative in vitro autoradiography.3H-AMPA binding sites were most concentrated in the hippocampus and cerebral cortex where glutamate receptors have been demonstrated to play a role in synaptic transmission. In aged rats,3H-AMPA binding sites in the hippocampus and cerebral cortex were not significantly changed. In our previous studies, it was noticed that strychnine-insensitive glycine receptors, which functionally coupled with NMDA receptors, showed marked age-dependent decreases in telencephalic regions. It has been shown that the glutamatergic neuronal system is involved in learning and memory. Nevertheless, it is considered that AMPA binding sites are not involved in the decline of neuronal functions, especially impairment of learning and memory, accompanying with aging process. 相似文献
18.
Regulation of neuronal ion channels via P2Y receptors 总被引:1,自引:0,他引:1
Within the last 15 years, at least 8 different G protein-coupled P2Y receptors have been characterized. These mediate slow metabotropic effects of nucleotides in neurons as well as non-neural cells, as opposed to the fast ionotropic effects which are mediated by P2X receptors. One class of effector systems regulated by various G protein-coupled receptors are voltage-gated and ligand-gated ion channels. This review summarizes the current knowledge about the modulation of such neuronal ion channels via P2Y receptors. The regulated proteins include voltage-gated Ca2+ and K+ channels, as well as N-methyl-d-aspartate, vanilloid, and P2X receptors, and the regulating entities include most of the known P2Y receptor subtypes. The functional consequences of the modulation of ion channels by nucleotides acting at pre- or postsynaptic P2Y receptors are changes in the strength of synaptic transmission. Accordingly, ATP and related nucleotides may act not only as fast transmitters (via P2X receptors) in the nervous system, but also as neuromodulators (via P2Y receptors). Hence, nucleotides are as universal transmitters as, for instance, acetylcholine, glutamate, or -aminobutyric acid. 相似文献
19.
The role of intracellular sodium in the regulation of NMDA-receptor-mediated channel activity and toxicity 总被引:2,自引:0,他引:2
Yu XM 《Molecular neurobiology》2006,33(1):63-79
Sodium (Na+) is the major cation in extracellular space and, with its entry into cells, may act as a critical intracellular second messenger
that regulates many cellular functions. Through our investigations of mechanisms underlying the activity-dependent regulation
of N-methyl-d-aspartate (NMDA) receptors, we recently characterized intracellular Na+ as a possible signaling factor common to processes underlying the upregulation of NMDA receptors by non-NMDA glutamate channels,
voltage-gated Na+ channels, and remote NMDA receptors. Furthermore, although Ca2+ influx during the activation of NMDA receptors acts as a negative feedback mechanism that downregulates NMDA receptor activity,
Na+ influx provides an essential positive feedback mechanism to overcome Ca2+-induced inhibition, thereby potentiating both NMDA receptor activity and inward Ca2+ flow. NMDA receptors may be recruited to cause excitoxicity through a Na+-dependent mechanism. Therefore, the further characterization of mechanisms underlying the regulation of NMDA receptors by
intracellular Na+ is essential to understanding activity-dependent neuroplasticity in the nervous system. 相似文献
20.
Summary Dopamine (DA) release from nerve terminals of the nigrostriatal DA neurons not only depends on the activity of nigral DA cells but also on presynaptic regulation. Glutamatergie neurons of cortical origin play a prominent role in these presynaptic regulations. The direct glutamatergic presynaptic control of DA release is mediated by N-methyl-D-aspartate (NMDA) and-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionate (AMPA) receptors, located on DA nerve terminals. In addition, by acting on striatal target cells, these glutamatergic neurons contribute also to indirect regulations of DA release involving several transmitters such as GABA, acetylcholine and neuropeptides. Diffusible messengers such as nitric oxide (NO) or arachidonic acid (AA) which are particularly formed under the stimulation of NMDA receptors may also participate to the regulation of DA release. In the present study, it will be shown that the co-application of NMDA and carbachol synergistically increases the release of [3H]-DA and that this effect is reduced by mepacrine or 4-bromophenacylbromide (107M), two inhibitors of PLA2. Therefore endogenously released AA induced by the co-stimulation of NMDA and cholinergic receptors seems to be involved, at least partly, in the release of DA. 相似文献