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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the effect of intrahippocampal administration of quinolinic acid (QUIN) on the temporal expression of mRNAs encoding the immediate early genes (IEGs) c-fos and NGFI-A, by in situ hybridization histochemistry. After administration of QUIN to the left hippocampus, expression of mRNA of both IEGs was transiently stimulated. Maximal expression was found between 1 and 3 h. mRNA of both IEGs was simultaneously expressed in the ipsilateral and contralateral sides in the granule cell layer of the dentate gyrus, the pyramidal cell layer of the CA1 and CA3 fields as well as in the cortex. After pretreatment with the non-competitive NMDA antagonist MK-801 (2 mg/kg i.p. -30 min) the increased expression of both IEGs was partially prevented in the hippocampus and completely in the cortex. No inhibition was observed after treatment with the AMPA antagonist NBQX (30 mg/kg i.p. -15, -5 and +10 min). Additional delayed expression of both IEGs was observed in the ipsilateral hippocampus. This expression was related to cell damage. Twelve h after QUIN administration, c-fos and NGFI-A mRNAs were present in the dentate gyrus. After 4 days, only c-fos mRNA was observed in the dentate gyrus and CA1 field while no NGFI-A mRNA was detected. The present results show that the effect of QUIN is mediated by NMDA and not by AMPA receptors.
Brain Res Mol Brain Res 1992 Nov
PMID:Administration of quinolinic acid in the rat hippocampus induces expression of c-fos and NGFI-A. 128 Dec 56

In a previous study [Shaw, C., Pasqualotto, B. and Lanius, R.A., Mol. Neuropharmacol., in press] we have shown that phosphorylation and dephosphorylation actions of protein kinase and alkaline phosphatase lead to decreases or increases in the number of GABAA and AMPA receptors in adult rat neocortex. Using the same in vitro cortical slice preparation, we have now examined the role of these enzymes in regulating GABAA and AMPA receptors at different stages of postnatal development. GABAA receptors were labelled with [3H]SR95531 [Shaw, C. and Scarth, B.A., Mol. Brain Res., 11 (1991) 273-282]; AMPA receptors were labelled with [3H]CNQX [Lanius, R.A. and Shaw, C., Mol. Brain Res., 15 (1992) 256-262]. At postnatal day 14, GABAA receptors showed a decrease in binding in response to alkaline phosphatase treatment as opposed to an increase in binding observed in response to protein kinase treatment. Similar effects were observed for AMPA receptors at 20 days of age. The direction of regulation following the enzyme treatments were opposite to those observed in the adult cortex for both receptor populations. These fundamental changes in the enzymatic nature of regulation for such key inhibitory and excitatory receptor populations in cortex may signal an important role for age-dependent kinases and phosphatases in the events leading to modifications in neuronal function during postnatal development.
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PMID:Reversible kinase and phosphatase regulation of brain amino acid receptors in postnatal development. 133 48

We have studied the effect of excitatory amino acids on the expression of mRNA for the immediate early genes c-fos, c-jun, jun-B, and NGF-1A in isolated cortical astrocytes. The expression of the different genes was induced by 100 microM kainate, quisqualate, AMPA and high concentrations of K+ (140 mM). NMDA did not induce the expression of any of the genes studied. The effect of quisqualate stimulation was not inhibited by the antagonist CNQX or by withdrawal of external Ca2+. In contrast the kainate effect was abolished by CNQX but not by the removal of external Ca2+. However, elevated K+ induced c-fos only when calcium was present in the external medium. These findings suggest that type-1 astrocytes lack NMDA receptors and that the induction of genes by quisqualate and kainate is in part independent of the presence of calcium in the external medium and may be mediated through second messenger pathways.
Brain Res Mol Brain Res 1992 Dec
PMID:Regulation of gene expression in astrocytes by excitatory amino acids. 133 35

We have recently shown that a high-affinity AMPA receptor labelled with the antagonist [3H]CNQX can be regulated in a 'living' cortical slice preparation by agonist stimulation or changes in electrical activity (Lanius, R.A. and Shaw, C. (1992) Anat. Rec., in press). Based on a study of GABAA receptors (Shaw, C. and Scarth, B.A. (1992) Mol. Brain Res., in press), which showed age-dependent changes in regulation, we have now investigated the regulation of high-affinity AMPA receptors in neocortex at different stages in postnatal development. The results show that regulation by agonist stimulation and increases in bioelectric activity are age-dependent in amount and, in the latter case, in direction. Agonist stimulation using quisqualate resulted in a significant receptor down-regulation of approximately 7% at ages less than 20 days postnatal; in adult rats quisqualate led to a significant 23% decrease. Changes in bioelectric activity induced by a combination of veratridine and glutamate showed a significant increase in AMPA receptor number of 16% at ages less than 20 days, whereas such treatment resulted in a significant 18% decrease in adult rats. The present data reveal a near mirror-image to the effects of veratridine and glutamate and agonist on GABAA receptors in the same preparation, but with a temporal mismatch in the amount and direction of regulation. We speculate that the age-dependent differences in direction of regulation for the receptor populations which serve key excitatory and inhibitory functions in cortex may provide a molecular basis for the gradual decline of neuronal plasticity during the critical period.
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PMID:Cortical AMPA receptors: age-dependent regulation by cellular depolarization and agonist stimulation. 135 59

The binding of (RS)-alpha-[3H]amino-3-hydroxy-5-methylisoxazole-4-propionic acid ([3H]AMPA), a selective ligand for non-N-methyl-D-aspartate excitatory amino acid receptors, was investigated in rat brain using an autoradiographic receptor binding technique. [3H]AMPA binding sites were widely distributed throughout the rat central nervous system, and the rank order of potency of displacers of [3H]AMPA binding was quisqualate greater than AMPA greater than 6,7-dinitroquinoxaline-2,3-dione = 6-cyano-7-nitroquinoxaline-2,3-dione greater than beta-N-oxalylamino-L-alanine greater than glutamate greater than kainate. Potassium thiocyanate (0-100 mM) exerted a 4-fold stimulation of [3H]AMPA binding, without changing the relative regional distribution of [3H]AMPA binding densities among rat brain regions. Scatchard analysis of equilibrium saturation binding revealed high affinity and low affinity components of [3H]AMPA binding, even in the absence of potassium thiocyanate. Addition of potassium thiocyanate increased the number of high affinity [3H]AMPA binding sites without a change in affinity. In addition, the number of low affinity [3H]AMPA binding sites was unchanged in the presence of potassium thiocyanate, but the affinity of low affinity [3H]AMPA binding was greatly increased. [3H]AMPA thus binds specifically to two affinity conformations of postsynaptic binding sites that appear to be interconverted with potassium thiocyanate. The pharmacologic profile of these sites is consistent with that of the ion channel-linked ("ionotropic") quisqualate/AMPA class of excitatory amino acid receptor in the rat central nervous system.
Mol Pharmacol 1992 May
PMID:Multiple states of rat brain (RS)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors as revealed by quantitative autoradiography. 137 15

A glutamate receptor was purified from Triton X-100-solubilized bovine cerebellum membranes. The purification was carried out in two steps: affinity chromatography using a spider toxin (Joro spider toxin; JSTX) immobilized on a lysine-agarose column, and a Mono Q anion exchange column. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of the purified active fraction showed a single band with Coomassie Blue staining, which migrated with a M(r) = 130,000. The specific [3H]amino-3-hydroxy-5-methyl-isoxazole propionate ([3H]AMPA) binding activity of the affinity-purified fraction was 2095-fold higher than that of the crude soluble fraction. Lineweaver-Burk plot analysis showed a Kd of 12.7 nM [3H]AMPA in the purified fraction. The purified fraction was examined with patch-clamp recording methods in reconstituted liposomes. A glutamate-activated channel was observed and was inhibited with JSTX. The rank order of potency of agonists inducing channel currents was AMPA = glutamate greater than quisqualate much greater than kainate greater than NMDA. Thus, there is strong evidence that the 130 kDa protein is a purified component of the native AMPA type glutamate channel of bovine cerebellum.
Brain Res Mol Brain Res 1992 May
PMID:Purification of AMPA type glutamate receptor by a spider toxin. 137 71

The binding of [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid ([3H]AMPA), a ligand for the quisqualate subtype of excitatory amino acid receptors, was measured after chemical modifications of rat brain synaptic membranes. Treatment with oxidizing or thiol-alkylating agents did not modify [3H]AMPA binding, whereas treatment with several sulfhydryl reagents produced marked increases in binding. The involvement of free sulfhydryl groups in the regulation of the properties of [3H]AMPA binding sites was suggested by the specificity of p-chloromercuribenzoic acid (PCMB), its sulfonate analog p-chloromercuriphenyl-sulfonic acid (PCMBS), and HgCl2, plus the reversal of their effects after reduction with dithiothreitol. Pretreatment of synaptic membranes with the oxidizing agent 5,5'-dithiobis(2-nitrobenzoic acid) or the alkylating agent N-ethylmaleimide did not significantly affect [3H]AMPA binding but markedly reduced the enhancing effect of PCMBS. On the other hand, the increase in [3H]AMPA binding produced by PCMBS was not prevented by treatment with agonists such as quisqualate or L-glutamate and was produced equally well in resealed postsynaptic membranes with both lipophilic or nonlipophilic SH-reagents. Using filtration assays, two types of binding sites could be detected with high and low affinity for [3H]AMPA. Treatment with SH-reagents produced an increase in the Bmax for the high affinity component and a decrease in the Bmax for the low affinity component, accompanied by an increase in its affinity for the ligand. Using centrifugation assays, the same two types of sites could be detected under control conditions but treatment with SH-reagents produced an increase in affinity of the large component that prevented the analytical differentiation of the two sites. Treatment with SH-reagents also increased the binding of [3H] glutamate to the N-methyl-D-aspartate receptors but did not modify the binding of [3H]kainate to the kainate receptors or the strychnine-insensitive [3H]glycine binding. These results suggest that free sulfhydryl groups allosterically modulate the affinity of the quisqualate subtype of excitatory amino acid receptors and also indicate that different types of glutamate receptors might be differentially affected by chemical modification.
Mol Pharmacol 1988 Aug
PMID:Effects of thiol-reagents on [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid binding to rat telencephalic membranes. 290 Oct 29

The distribution of AMPA-selective subunits, GluR1-4, was determined in the human hippocampus and cerebellum by in situ hybridization and immunocytochemistry. In the hippocampus, in situ hybridization revealed that GluR1 and GluR2 mRNAs were similarly distributed and highly expressed in the dentate gyrus, with lower levels in the CA regions. GluR3 and GluR4 mRNAs were expressed at very low levels. Immunocytochemical studies showed that GluR1- and GluR2/3-immunoreactivity were highest in the dentate molecular and granular layers. In the CA regions, GluR1 and GluR2/3 staining was observed in pyramidal cell bodies and surrounding neuropil and was more intense in CA4/3/2 compared with CA1. GluR4-immunoreactivity was low throughout the hippocampus. In the cerebellum, GluR1 and GluR4 transcripts were expressed in the granular and Purkinje cell/Bergmann glia layers. GluR2 mRNA was highly expressed in the granular layer and individual Purkinje cells, while GluR3 mRNA was not detectable in the cerebellum. GluR1- and GluR4-immunoreactivity were localized to Purkinje cells and putative Bergmann glia, as well as their processes extending into the molecular layer. GluR2/3 staining was intense in Purkinje cells, with moderate staining in the granular layer. Thus, GluR1-4 subunits are differentially distributed in the hippocampus and cerebellum. In addition, the distribution of subunit mRNA and protein correlate well with each other and with the glutamatergic neuroanatomy of the hippocampus and cerebellum.
Brain Res Mol Brain Res 1995 Jul
PMID:Distribution of AMPA-selective glutamate receptor subunits in the human hippocampus and cerebellum. 747 26

An AMPA-type glutamate receptor cDNA, GFGR52, was cloned from a goldfish retinal cDNA library. GFGR52 is highly homologous to the AMPA D-FLOP-type glutamate receptor. In situ hybridization revealed GFGR52 gene expression in both retinal ganglion cells and optic tectum. This expression was reduced during optic nerve regeneration and this decreased level of gene expression lasted until the reinitiation of synaptogenesis. These findings suggest that interactions between optic nerve and its target, the optic tectum are necessary for maintaining AMPA D-type glutamate receptor gene expression in both retinal and tectal neurons.
Brain Res Mol Brain Res 1995 Aug
PMID:Down-regulation of AMPA-type glutamate receptor gene expression during goldfish optic nerve regeneration. 749 54

The effect of the ionotropic glutamate receptor agonist, AMPA, on intracellular Ca2+ concentrations ([Ca2+]i) was studied in dopaminergic neurons present in primary cultures of ventral tegmental mesencephalon of 14 day rat embryos. Exposure of cells to 10 microM AMPA for 1 min increased [Ca2+]i by 2-3 fold in dopaminergic and other neurons and this response was obliterated within 5 min by superfusion with AMPA-free incubation buffer. In dopaminergic neurons, 1 min or 5 min exposure to 50 microM AMPA increased [Ca2+]i 3 to 5 times over control values. This rise in [Ca2+]i persisted even after a 20 min superfusion with AMPA-free media, whereas, [Ca2+]i in non-dopaminergic neurons was reversed to control values during this time. Preincubation (2 min) of cultured cells with NBQX or the L-type channel blocker, nifedipine, but not with MK-801 blunted the rise of [Ca2+]i in dopaminergic and other neurons. Pretreatment with 2 microM NBQX shifted the dose response curve for AMPA to the right without changing the basal [Ca2+]i. The presence of 10 microM dantrolene, a blocker of Ca2+ release from intracellular stores, did not alter the initial rise of [Ca2+]i elicited by 50 microM AMPA, but prevented the destabilization of Ca2+ homeostasis by facilitating the recovery to normal of basal [Ca2+]i. Exposure to 50 microM AMPA (5 min) caused an irreversible increase of [Ca2+]i in dopaminergic neurons and cell death was manifested by propidium iodide uptake 6-7 h after AMPA exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
Brain Res Mol Brain Res 1994 Feb
PMID:Persistent AMPA receptor stimulation alters [Ca2+]i homeostasis in cultures of embryonic dopaminergic neurons. 751 76


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