Disease relevance of GRIA1

• alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA), kainate and N-methyl-D-aspartate (NMDA) receptors represent major classes of glutamate receptors (GluR) which play fundamental roles in normal excitatory synaptic activity and, probably, in the etiology of several brain diseases [1].
• Expression of human glutamate receptors (GluR) in neuroblastoma cell lines [2].
• The aim of this study was to examine the distribution of mRNAs for the subunits of the AMPA type of glutamate receptor (GluR A, B, C and D) in control human spinal cord using in situ hybridization and to examine in parallel the expression of these mRNAs in patients with sporadic amyotrophic lateral sclerosis (ALS) [3].
• Ischemia induced a marked down-regulation of GluR2 mRNA and a small down-regulation of GluR1 mRNA in CA1 at 2 days, as assessed by quantitative in situ hybridization [4].
• Hypothermia prevented ischemia induced changes in GluR1 mRNA expression [4].

Psychiatry related information on GRIA1

• In situ hybridization experiments showed that human GluR1 mRNA is present in granule and pyramidal cells in the hippocampal formation and that there is no apparent difference of distribution between control patient and patient with Alzheimer's disease [5].
• Therefore, together with further investigations on their potential functional consequences, we propose a thorough exploration of aAbs to MDOR and to AMPA GluR1 subunit as early biomarkers signaling opiate addiction [6].
• Here, we used herpes simplex virus vectors to examine how transient increases in the expression of GluR1 or GluR2 protein in the shell component of NAc affect the rewarding impact of electrical stimulation of the medial forebrain bundle, as reflected by intracranial self-stimulation (ICSS) thresholds in rats [7].
• Following 1, 2, 4 and 7 days' exposure, plants were monitored for uranium uptake, biometric parameters, capacities of enzymes involved in the anti-oxidative defense mechanisms (GPOD, SPOD, GLUR, SOD, ICDH, G-6P-DH), glutathione (GSH) pool and DNA integrity [8].
• However, the roles of D1 receptors, CREB, and GluR1 in morphine dependence are not well understood [9].

High impact information on GRIA1

• In this study, we have shown a decrease in HIV-infected brain of the expression of mRNA and protein of the GluR-A flop subtype of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) glutamate receptor in cerebellar Purkinje cells [10].
• This effect was not diminished by mutating the CaMKII phosphorylation site on the GluR1 AMPA-R subunit, but was blocked by mutating a predicted PDZ domain interaction site [11].
• These results show that LTP and CaMKII activity drive AMPA-Rs to synapses by a mechanism that requires the association between GluR1 and a PDZ domain protein [11].
• Insertion of this exon cassette into the COOH-terminus of the GluR1 AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate) receptor was sufficient to cause GluR1 to be localized to discrete, receptor-rich domains [12].
• The steady-state current-voltage (I-V) relations of glutamate- and kainate-induced currents through homomeric channels fell into two classes: channels composed of either the GluR-A, -C, and -D subunits showed doubly rectifying I-V curves, and channels composed of the GluR-B subunits displayed simple outward rectification [13].

Chemical compound and disease context of GRIA1

• We used in situ hybridization to examine GluR1, GluR2, and GluR3 messengerRNAs (encoding alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid/kainate receptor subunits) in sections of autopsy samples of Alzheimer's disease brains and age-, sex-, and post-mortem delay-matched brains from non-demented (control) subjects [14].
• STN-HFS-induced forelimb dyskinesia was blocked by microinjection of the Glu receptor antagonist kynurenate into the SNr and facilitated by microinjection of a mixture of the Glu receptor agonists AMPA and NMDA into the SNr [15].

Biological context of GRIA1

• Characterization of multiple phosphorylation sites on the AMPA receptor GluR1 subunit [16].
• Southern and PCR analysis of a somatic cell-hybrid panel mapped HBGR1 to human chromosome 5q31.3-33.3 and mapped HBGR2 to chromosome 4q25-34 [17].
• This was accomplished with genomic clones containing putative human homologs of rat GluR 1-4 isolated by high-stringency screening of a cosmid library with the rat cDNAs encoding GluR1-4 [18].
• RNA editing plays an important role in determining physiological characteristics of certain glutamate-gated receptor (GluR) channels such as Ca2+ permeability and desensitization kinetics [19].
• Finally, the GluR1/GluR2 messenger RNA ratios increase in the aged hippocampus, particularly in the CA3 subfield, suggesting that altered calcium homeostasis may contribute to age-related neuronal death [20].

Anatomical context of GRIA1

• In contrast, intense GluR1 labeling was observed in a small subpopulation of interneurons and low GluR1 immunoreactivity was present in many other cortical neurons [21].
• The aim of the present study was to determine quantitatively GluR subunit combinations in the human temporal neocortex by double-labeling immunocyto- chemical experiments [1].
• Results revealed statistically significant increases in the NAc, but not in the putamen, of NMDA receptor subunit (NR)1 and glutamate receptor subunit (GluR)2/3 wit trends in GluR1 and GluR5 in COD [22].
• This study investigated whether the AMPA receptor subunit content (GluR1, GluR2, GluR2/3) within "vulnerable" vs. "resistant" sectors of the hippocampus is quantitatively altered with increasing AD neuropathology, as determined by Braak staging [23].
• Motor neurons in the spinal cord, brainstem, and motor cortex were relatively strongly immunoreactive with the GluR2/3 subunit antibody, moderately so with the GluR4 subunit antibody, and showed relatively low levels of immunoreactivity with the GluR1 subunit antibody [24].

Associations of GRIA1 with chemical compounds

• However, in rhesus monkeys chronically treated with antipsychotic drugs, clozapine treatment significantly decreased GRIA1 and increased GRIA3 mRNA expression, while both clozapine and haloperidol increased the expression of GRIA2 subunit mRNA [25].
• We have characterized the phosphorylation of the glutamate receptor subunit GluR1, using biochemical and electrophysiological techniques [16].
• It is suggested that the positive charge contributed by the arginine of the edited GluR-B(R) subunit determines low divalent permeability in heteromeric GluR channels and that changes in GluR-B(R) expression regulate the AMPA receptor-dependent divalent permeability of a cell [26].
• Cyclic AMP-dependent protein kinase specifically phosphorylates SER-845 of GluR1 in transfected HEK cells and in neurons in culture [16].
• These results indicate that clone HBGR1 codes for a glutamate receptor of the kainate subtype cognate to members of the glutamate receptor family from rodent brain [17].

Physical interactions of GRIA1

• The present study was performed to elucidate whether SGK3 and stargazin interact or are effective through different pathways in the regulation of GluR1 [27].
• This structure will predominate if GluR1 binds to GluR2 more rapidly during receptor assembly than other subunit combinations [28].
• Crystal structure of the second PDZ domain of SAP97 in complex with a GluR-A C-terminal peptide [29].

Enzymatic interactions of GRIA1

• Pretreatment with WAY-100635 counteracted the NBQX effects and restored the initial learning-specific increase in Ca2+/calmodulin-dependent protein kinase II (CaMKII) function and the later increase in GluR2/3 and phosphorylated GluR1 surface expression [30].
• However, activity-dependent phosphorylation of substrates at synapses was highly selective in that the glutamate receptor subunits NR2B and GluR1 were poorly phosphorylated whereas PSD-95 and Stargazin, proteins implicated in the scaffolding and trafficking of AMPA receptors, were robustly phosphorylated [31].

Regulatory relationships of GRIA1

• In conclusion, SGK3 and stargazin regulate GluR1 independently, and thus, their effects on glutamate-induced currents are additive [27].
• The L-glutamate EC50 was 10.2 microM when wild-type GluR-A was coexpressed with GluR-B (GluR-A/B) and 38.9 microM when GluR-A445Q/B449Q receptors were tested [32].
• The anesthetic 1-chloro-1,2,2-triflurocyclobutane (F3) weakly inhibited kainate responses in oocytes expressing GluR3 receptors but not oocytes expressing GluR1 or GluR2+3 receptors [33].
• When CXCR2 was expressed with the AMPA-type glutamate receptor GluR1, CXCR2 dimerization was again impaired in a dose-dependent way, and receptor functions were prejudiced [34].
• Stimulation of synaptic NMDA receptors by a protocol that induces chemical LTP resulted in a long-lasting reduction in the mobility of spine CaMKIIalpha and an increased mobile fraction but slower kinetics for spine GluR1 [35].

Other interactions of GRIA1

• Fractional calcium currents through recombinant GluR channels of the NMDA, AMPA and kainate receptor subtypes [36].
• We have investigated the subtype selectivity of these compounds by examining their binding affinity for homomeric hGluR1, -2, -4, or -5 (and hGluR6 in the case of 5-iodowillardiine (22)) [37].
• 5-Fluorowillardiine (19) has higher affinity than AMPA for both homomeric hGluR1 and hGluR2 and compared to AMPA displays greater selectivity for AMPA receptor subtypes over the kainate receptor, hGluR5 [37].
• Recovery from desensitization varied between 3.1 ms (GluR4 flip) and 178 ms (GluR1 flip) [38].
• The prevalence of the NR2B subunit in thalamo-amygdaloid spines provides morphological evidence supporting its role in the fear conditioning circuit while the differential distribution of the GluR subtypes may reflect distinct roles for their involvement in this circuitry and synaptic plasticity [39].

Analytical, diagnostic and therapeutic context of GRIA1

• The localization and expression of ionotropic non-N-methyl-D-aspartate glutamate receptors (GluR) were investigated in the developing and adult rat cerebellum using subunit-specific polyclonal antibodies for immunocytochemical, immunoblot and immunoprecipitation studies [40].
• Presently, the kinetics of activation, desensitization and recovery from desensitization of human AMPARs (GluR1, 3 and 4 flip and flop, and GluR2 flip and flop in R and G edited forms, respectively) transiently expressed in HEK293 cells were studied with patch-clamp techniques and ultra fast agonist application [38].
• We have quantitated the protein levels of alpha-amino-isoxazolepropionic acid (AMPA)-type (GluR1) and N-methyl-D-aspartate-type (NMDAR1) glutamate receptors in postmortem brain tissues of patients with Alzheimer's disease and age-matched controls using western blotting [41].
• Gating was studied using ultra-fast drug perfusion of outside-out patches containing rat GluR-A or GluR6 subunits excised from transfected human embryonic kidney cells [42].
• Interestingly, levels of a postsynaptic density protein named SAP97, which recognizes and potentially masks the epitope region of GluR1, was positively correlated with those of GluR1 protein in the control group, but not in the patient group [41].

References