Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Retinal neurons that express the immediate early gene c-fos after light exposure were characterized by neurotransmitter content using histochemical and immunocytochemical staining. In Northern blots the amount of c-fos mRNA peaked at 30 min, but remained detectable 60 min following light stimulation. Fos proteins were seen in the inner nuclear and ganglion cell layers, and the staining was most intense two and three hours after beginning the light exposure. In the ganglion cell layer 30-40% of Fos-immunoreactive cells were cholinergic displaced amacrine cells and 3-5% were ganglion cells. In the inner nuclear layer 24% of Fos-immunoreactive cells were Type I and 7% Type II NADPH-diaphorase-reactive (nitric oxide synthase) amacrine cells, 11% were tyrosine hydroxylase-containing cells, and 10-15% cholinergic amacrine cells. No Fos immunoreactivity was seen in serotoninergic, somatostatin- or VIP-immunoreactive cells, bipolar, horizontal or photoreceptor cells. Nicotine, kainic acid, NMDA and SCH 38393, a dopamine D1 receptor agonist, induced Fos immunostaining in the inner nuclear and ganglion cell layers, but administration of the corresponding receptor blockers mecamylamine, kynuretic acid, MK-801, haloperidol and SCH 23990 did not prevent light-induced Fos expression.
Brain Res Mol Brain Res 1995 Mar
PMID:Light-induced c-fos expression in amacrine cells in the rabbit retina. 777 1

Different NMDA receptor subunits have been recently cloned. The present paper describes the developmental profile of expression of the NR-1 subunit and three NR-2 subunits (A, B, C) in the rat central nervous system. A sensitive RNase protection assay was employed to determine simultaneously the mRNA levels of these receptor subunits. We found low levels of NR-1 mRNA (comprising all different splicing isoforms) in newborn rats with a progressive increase of its expression in the following 2-3 weeks. NR-2 subunits can be regarded as 'modulatory' since their expression can produce differences in the properties of NMDA receptors. More than one NR-2 subunits can be expressed in the same brain region. NR-2A and NR-2C are concomitantly expressed in the cerebellum and during development their mRNAs increase with a similar profile from low levels in P-8 rats to maximal expression in P-21 animals. NR-2A and NR-2B are concomitantly expressed in several brain regions with a different ontogenetic profile. In the hippocampus NR-2B mRNA increases rapidly during the first week of life as compared to the NR-2A subunits which at this time is expressed to low levels indicating that NR-2B will probably be dominant in determining the NMDA properties during the first period of life. Our data can provide a molecular correlate with properties of NMDA receptors such as voltage dependent Mg2+ block and deactivation kinetics which undergo significant changes during development and have been shown to depend upon the NR-2 subunit co-expressed with the common NR-1 subunit in various brain regions.
Brain Res Mol Brain Res 1994 Sep
PMID:Regulation of NMDA receptor subunit mRNA expression in the rat brain during postnatal development. 780 19

Intrahippocampal injection of the endogenous excitotoxin quinolinic acid (QUIN) induces seizures together with local, delayed neurodegeneration in specific cell layers. In situ hybridization histochemistry was used to study the spatio-temporal pattern of expression of neurotrophins (NTFs) after this treatment. As in other excitatory paradigms, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) mRNA levels increased dramatically and transiently in dentate gyrus after the administration of 120 nmol of QUIN to the left hippocampus. BDNF, but not NGF, mRNA also increased in the hippocampal pyramidal cell layer, mainly in the CA1 field. Neurotrophin-3 (NT3) mRNA levels decreased in dentate gyrus, practically disappeared around 12 h after the insult and returned to basal levels four days later. A very different pattern of expression of NTFs was found locally: (a) upregulation of NGF and BDNF mRNAs expression was prevented in a spherical region of 1-2 mm diameter around the injection site, (b) a delayed increase in NT3 mRNA levels, beginning at 12 h and lasting for at least 4 days after the administration of QUIN, was found in the same region, in cell layers showing neurodegeneration. Pretreatment with the non-competitive NMDA antagonist MK-801 (2 mg/kg, 30 min before the insult), partially blocked the increase in both BDNF and NGF mRNAs, as well as the decrease in NT3, in the contralateral hippocampus. However, this treatment did not prevent the QUIN-induced local downregulation of NGF and BDNF. Treatment with the AMPA/kainate antagonist NBQX (30 mg/kg, 15 and 5 min before, and 10 min after the insult) did not influence the effect of QUIN upon NGF or BDNF mRNA levels, although it partially prevented the hippocampal contralateral decrease in NT3 mRNA. In conclusion, the present study strongly supports previous work concerning different regulation of BDNF/NGF respect to NT3 in seizure inducing paradigms. Moreover, the different and to some extent opposite regulation of NTFs in the hippocampal region contiguous to the injection site, respect to the remaining hippocampus, suggests a differential regulation of NTFs in QUIN-induced neurodegenerative and seizural processes. Finally, our pharmacological data, (i) show that the upregulation of NGF and BDNF mRNAs, indirectly induced by QUIN, is not mediated by AMPA receptors, and (ii) suggest other effects for QUIN, apart from the stimulation of NMDA receptors.
Brain Res Mol Brain Res 1994 Oct
PMID:Differential regulation of the expression of nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 mRNAs in adult rat brain after intrahippocampal injection of quinolinic acid. 785 71

We investigated the expression of NMDA receptors within the brainstem circuit controlling esophageal swallowing using transneuronal viral labeling and in situ hybridization. Neurons of the central subnucleus of the nucleus solitary tract (NTScen) are interneurons linking vagal afferents with esophageal motoneurons in the compact formation of the nucleus ambiguus (NAc). Following injections of Pseudorabies virus (PRV) into rat esophagus and incubation with NMDAR1 cRNA, neurons infected with PRV localized to the NAc and NTScen expressed NMDAR1 mRNA.
Brain Res Mol Brain Res 1994 Dec
PMID:NMDAR1 mRNA expression in the brainstem circuit controlling esophageal peristalsis. 789 19

The subcellular processes that correlate with early learning and memory formation in the chick and sensitive periods for this learning are discussed. Imprinting and passive avoidance learning are followed by a number of cellular processes, each of which persists for a characteristic time in certain brain regions, and may culminate in synaptic structure modification. In the chick brain, the NMDA subtype of glutamate receptor appears to play an important role in both memory formation and sensitive periods during development, similar to its demonstrated role in neural plasticity in the mammalian brain. Two important findings have emerged from the studies using chickens. First, memory formation appears to occur at multiple sites in the forebrain and, most importantly, it appears to "flow" from one site to another, leaving neurochemical traces in each as it moves on. Second, the memory is laid down either in different sites or in different subcellular events in the left and right forebrain hemispheres. Hence, we are alerted to the possibility of similar asymmetrical processes occurring in memory consolidation in the mammalian brain. The similarities between early memory formation and experience-dependent plasticity of the brain during development are discussed.
Mol Neurobiol
PMID:The molecular neurobiology of early learning, development, and sensitive periods, with emphasis on the avian brain. 791 26

In the present study, we have attempted to clarify whether neuroblastoma glioma hybrid NG 108-15 cells (NG cells) possess the NMDA receptor complex using [45Ca2+]influx and [3H]MK-801 binding as functional measures. Glutamate and NMDA dose-dependently increased [45Ca2+]influx and these increases were further enhanced by glycine. Scatchard analysis revealed the presence of a high-affinity binding site for [3H]MK-801 with a KD of 18.8 nM and a Bmax of 0.328 pmol/mg protein. This [3H]MK-801 binding was also increased by NMDA in a dose-dependent manner and this increase was further enhanced by glycine. Both ketamine and MK-801 inhibited glutamate- and NMDA-induced [45Ca2+]influx as well as the increase of [3H]MK-801 binding in a dose-dependent manner. Similarly, Mg2+ and Zn2+ dose-dependently reduced both glutamate-induced [45Ca2+]influx and [3H]MK-801 binding. Spermine, one of the polyamines, showed a biphasic stimulatory effects on glutamate-induced [45Ca2+]influx and [3H]MK-801 binding. These results indicate that NG cells possess a pharmacologically distinct NMDA receptor complex and suggest that these cells may be useful for the analyses on pharmacological and biochemical characteristics of the NMDA receptor complex.
Brain Res Mol Brain Res 1994 Mar
PMID:Presence of N-methyl-D-aspartate (NMDA) receptors in neuroblastoma x glioma hybrid NG108-15 cells-analysis using [45Ca2+]influx and [3H]MK-801 binding as functional measures. 791

An antagonist ligand for the glycine site of the NMDA receptor, [3H]L-689,560, has recently been described. We have investigated the use of this ligand to label NMDA receptors which have been solubilized from rat brain. It has significant advantages over [3H]dizocilpine ([3H]MK-801) for this purpose since (a) it is not inhibited by most detergents, (b) interactions between the glutamate and glycine sites are maintained, and (c) equilibrium binding is rapid and of high affinity (Kd = 8.8 +/- 1.9 nM, n = 4). Nevertheless, precautions must be taken to remove glycine throughout all experimental procedures. In addition we have investigated the ability of NMDA receptors to bind to various lectins and conclude that only N-linked glycosylation is present, consistent with consensus sequences for glycosylation present in cloned subunits of the NMDA receptor. Further binding of the radioligand [3H]L-689,560 was detected both to the solubilized receptor and to receptor immobilized on lectin-agarose, identifying it as an appropriate ligand for use in the characterization of NMDA receptors during purification procedures.
Mol Membr Biol
PMID:Characterization of the solubilized NMDA receptor complex from rat brain with [3H]L-689,560, a glycine site antagonist. 791 9

Changes in cytosolic Na+ ([Na+]i) caused by a toxic glutamate (GLU) or NMDA treatment of cultured hippocampal neurons were monitored by using SBFI fluorescent probe and imaging microscopy. Both GLU and NMDA (50 or 100 microM in Mg(2+)-free solution, 15 min) induced a marked increase in [Na+]i (from 6-8 to 30-45 mM) which persisted after the termination of a treatment. The competitive NMDA antagonist, APV (100 microM) when applied in the post-NMDA period failed to decrease the elevated [Na+]i. The results obtained strongly suggest that the main reason for an impairment of Na+/Ca2+ exchange in the post-glutamate period (see Febs Letters 1993, 324, 271-273) is a reduction of the transmembrane Na+ gradient caused apparently by inhibition of Na(+)-K+ pump.
Biochem Mol Biol Int 1994 Mar
PMID:Changes in cytosolic sodium caused by a toxic glutamate treatment of cultured hippocampal neurons. 791 64

The increased levels of proenkephalin mRNA in the dentate gyrus following hippocampal stimulation have been assumed to be a consequence of the transient induction of c-fos. Injection of 50 microM NMDA in vivo onto the dendrites of a small number of granule cells causes a pronounced but highly localised elevation in proenkephalin mRNA levels 24 h later, whereas vehicle has no effect. In contrast, there is a widespread induction of c-fos mRNA throughout the dentate gyrus, 45 min after injection of either vehicle or NMDA, suggesting that induction of c-fos expression is unrelated to the subsequent, anatomically discrete, increase in proenkephalin mRNA levels.
Brain Res Mol Brain Res 1994 Aug
PMID:Induction of c-fos gene expression is not responsible for increased proenkephalin mRNA levels in the hippocampal dentate gyrus following NMDA stimulation. 798 41

We have examined the effects of oxidizing and reducing agents and sodium nitroprusside (SNP) on currents evoked by NMDA (N-methyl-D-aspartate) using the Xenopus oocyte expression system. Oocytes were injected with RNA prepared from either whole rat brain or from the NMDAR1 clone recently isolated from rat brain. Bath application of 1-1000 microM SNP, which releases nitric oxide and ferrocyanide, caused a rapid inhibition of NMDA-evoked current in both preparations. The inhibitory effect reversed spontaneously within 15 min. Kainate responses were not affected by SNP. Exposure to the reducing agent, dithiothreitol (DTT), enhanced NMDA currents; the oxidant, 5,5-dithio-bis-2-nitrobenzoic acid (DTNB), inhibited NMDA responses, as has been observed in other preparations. The site of action of SNP appeared to be different than the DTT/DTNB redox site for several reasons: SNP and DTNB inhibitions were additive at high doses, DTT did not rapidly reverse SNP effects, and SNP and DTT treatments did not show the same susceptibility to block by the NMDA antagonist, aminophosphonovaleric acid (APV). The results demonstrate that modulation of NMDA receptors by SNP is a property of homomeric channels and is retained when the NMDAR1 subunit is expressed in oocytes.
Brain Res Mol Brain Res 1994 Mar
PMID:Effects of nitroprusside and redox reagents on NMDA receptors expressed in Xenopus oocytes. 801 97


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>