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

A cDNA encoding a novel human glutamate receptor subunit protein was isolated from a human hippocampal library. This cDNA, termed humEAA2, is most closely related to rat cDNAs for kainate receptor proteins and, when expressed in COS cells, is associated with high affinity kainate receptor binding. The relative potency of compounds in displacing [3H]kainate binding was kainate greater than quisqualate greater than domoate greater than L-glutamate much greater than 6,7-dinitroquinoxaline-2,3-dione greater than dihydrokainate greater than 6-cyano-7-nitroquinoxaline-2,3-dione greater than (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid. Homomeric expression of humEAA2 does not appear to elicit ligand-gated channel activity. Nevertheless, the molecular structure and pharmacology of high affinity kainate binding suggest that humEAA2 is a novel subunit protein of a human kainate receptor complex.
Mol Pharmacol 1992 Jul
PMID:Molecular structure and pharmacological characterization of humEAA2, a novel human kainate receptor subunit. 132 49

A high-affinity sodium-dependent L-glutamate transporter was expressed in Xenopus oocytes after microinjection of poly(A)+ RNA from primary astrocyte cultures from rat brain cortex. mRNA-induced L-glutamate transport was saturable by substrate and shows kinetic features similar to those found in intact glial cell preparations. L-Glutamate accumulation was prevented by rising the external K+ concentration or by coincubation with L-, D-aspartate or D-glutamate. After fractionation by sucrose density gradient, the mRNA encoding for the expressed L-glutamate transporter from glial cells was found in fractions containing messages of 2.05-2.9 kilobases (kb) in length.
Brain Res Mol Brain Res 1992 Sep
PMID:L-glutamate transporter derived from mRNAs of primary glial cultures: expression in Xenopus laevis oocytes. 133 63

The gene encoding chick cerebellar Bergmann glia-specific kainate binding protein (chKBP), has been isolated, characterized and expressed in heterologous systems. The structural gene spans 11.2 kb and contains 11 exons and 10 introns. Several of the exons encode specific receptor domains, including each of the predicted transmembrane regions. Exon/intron boundaries flanking the second, putative channel-forming transmembrane domain are conserved between chKBP and other glutamate/kainate receptor subunits. The putative promoter region 5' to the first exon displays high GC content and TATA, CAAT and AP1 consensus sequences. Transcription of the chKBP gene is evident prior to full cerebellar cortical maturation. Transcripts are abundant in cells consistent with Bergmann glia, as revealed by in situ hybridization. Transfection of 293 kidney cell cultures with chKBP cDNA or chKBP gene expression constructs confers CNQX-sensitive kainate binding with the pharmacological specificity displayed by both chKBP and kainate receptors. However, expression of the same constructs in Xenopus oocytes fails to yield detectable agonist-activated currents.
Brain Res Mol Brain Res 1992 Dec
PMID:Organization and expression of the gene encoding chick kainate binding protein, a member of the glutamate receptor family. 133 27

Electrical recordings were made to characterize the sensitivity of Xenopus oocytes to changes in extracellular pH, and to determine whether rat cerebral cortex poly(A)+ RNA (mRNA) expressed GABAB receptors with atypical electrical properties. All oocytes showed some sensitivity to changes in pH, and those from a small fraction (< 10%) of frogs were found to be highly responsive to acidification of bathing Ringer. In these oocytes, reduction in extracellular pH elicited membrane current responses with two components: (1) Smooth, maintained currents, primarily associated with a decrease in K+ conductance. (2) Oscillatory Cl- currents, elicited through activation of the phosphoinositide/Ca2+ messenger pathway. Oocytes with highest levels of sensitivity responded to decreases as low as 0.1 pH unit (Ringer pH 7.0 lowered to pH 6.9). Rat cortex mRNA consistently showed strong expression of membrane current responses mediated by GABAA, glutamate, kainate, serotonin and acetylcholine (muscarinic) receptors, together with responses mediated by a variety of neuropeptide receptors. In these oocytes, enantiomers of the GABAB receptor agonist baclofen, at concentrations ranging between 1 microM and 10 mM (pH 7.0), activated no significant membrane current responses. However, at concentrations > 0.1 mM hydrochloride salts of baclofen caused appreciable acidification of Ringer solutions; for example, 1 mM baclofen lowered pH from 7.0 to 6.0. Thus, when assaying oocytes with high sensitivity to pH, failure to make the necessary re-adjustment could result in apparent baclofen responses that, in reality, are simply due to pH effects alone.(ABSTRACT TRUNCATED AT 250 WORDS)
Brain Res Mol Brain Res 1992 Dec
PMID:Sensitivity of Xenopus oocytes to changes in extracellular pH: possible relevance to proposed expression of atypical mammalian GABAB receptors. 133 30

In primary cultures of neurons from cerebral cortex and striatum, 30 s stimulation with the excitatory amino acid glutamate elicited a 5 to 9-fold increase in immediate early gene (IEG) mRNAs. Glutamate increased c-fos, c-jun, jun-B, and NGFI-A (zif/268) mRNAs by binding to both alpha-amino-3-hydroxy-5-methylisoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor types, and increased c-fos, jun-B, and NGFI-A mRNAs by binding to the metabotropic receptor. NMDA receptor activation elicited IEG expression by a transmembrane calcium influx; AMPA receptor-induced depolarization played a permissive role for the opening of the NMDA receptor channel. The protein kinase C (PKC) inhibitor H-7 (but not inhibitors of cyclic nucleotide-dependent and calcium/calmodulin-dependent protein kinases) partially blocked IEG expression induced by glutamate.
Brain Res Mol Brain Res 1992 Jan
PMID:Differential induction of immediate early genes by excitatory amino acid receptor types in primary cultures of cortical and striatal neurons. 134 32

A Saccharomyces cerevisiae glutamate auxotroph, lacking NADP-glutamate dehydrogenase (NADP-GDH) and glutamate synthase (GOGAT) activities, was complemented with a yeast genomic library. Clones were obtained which still lacked NADP-GDH but showed GOGAT activity. Northern analysis revealed that the DNA fragment present in the complementing plasmids coded for a 1.5kb mRNA. Since the only GOGAT enzyme so far purified from S. cerevisiae is made up of a small and a large subunit, the size of the mRNA suggested that the cloned DNA fragment could code for the GOGAT small subunit. Plasmids were purified and used to transform Escherichia coli glutamate auxotrophs. Transformants were only recovered when the recipient strain was an E. coli GDH-less mutant lacking the small GOGAT subunit. These data show that we have cloned the structural gene coding for the yeast small subunit (GUS2). Evidence is also presented indicating that the GOGAT enzyme which is synthesized in the E. coli transformants is a hybrid comprising the large E. coli subunit and the small S. cerevisiae subunit.
Mol Microbiol 1992 Feb
PMID:Cloning of a yeast gene coding for the glutamate synthase small subunit (GUS2) by complementation of Saccharomyces cerevisiae and Escherichia coli glutamate auxotrophs. 134 1

Excitatory amino acids (EAAs) can potently modulate gonadotropin secretion in the male rat and monkey. In the present study we examined the effect of EAAs on luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in the female rat under low estrogen (ovariectomized) and high estrogen (proestrus) backgrounds. In ovariectomized immature female rats N-methyl-D-aspartate (NMDA) inhibited LH but not FSH secretion at 30 min post-injection. In contrast, NMDA potently stimulated LH but not FSH secretion when administered on proestrus to adult female rats. Both glutamate and kainate were also found to stimulate LH but not FSH secretion in estrogen-treated ovariectomized immature rats. This study suggests that EAA neurotransmission may be an important component in the expression of gonadotropin surges and that EAA effects appear to be subject to gonadal steroid regulation.
J Steroid Biochem Mol Biol 1992 Mar
PMID:Excitatory amino acid regulation of gonadotropin secretion: modulation by steroid hormones. 134 28

A new crystal form of the hexameric NAD(+)-linked glutamate dehydrogenase (GDH) from Clostridium symbiosum has been grown using the hanging drop method of vapour diffusion. The crystals are obtained either by using high concentrations of the amino acid substrate of the enzyme, glutamate, as the precipitant or by co-crystallization from ammonium sulphate in the presence of either p-chloromercuribenzene sulphonate or potassium tetracyanoplatinate. The crystals diffract well and X-ray photographs have established that they are in the space group R32. Considerations of the values of Vm indicate that the asymmetric unit of the R32 crystals contains a single subunit. Packing considerations based on the structure of the native enzyme determined from a different crystal form suggest that the molecule must undergo a significant conformational change in order to be accommodated in the new cell. Such a conformational rearrangement may represent an important step in the catalytic cycle.
J Mol Biol 1992 Apr 20
PMID:Effect of additives on the crystallization of glutamate dehydrogenase from Clostridium symbiosum. Evidence for a ligand-induced conformational change. 134 42

The pharmacological actions of L-proline on excitatory and inhibitory amino acid receptors have been characterized under voltage-clamp conditions, using cultured dissociated neurons from the dorsal horn of the rat spinal cord. At a holding potential of -62 mV, millimolar concentrations of L-proline elicited an inward current that was partially antagonized by D-(-)-2-amino-5-phosphonopentanoic acid (APV), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and strychnine and was virtually abolished (97% block) by a combination of all three antagonists. Currents evoked by D-proline were abolished by strychnine alone. APV-, CNQX-, and strychnine-sensitive components of L-proline-evoked currents were isolated using various combinations of the three antagonists. These currents were identical to currents elicited by N-methyl-D-aspartate (NMDA), kainate, and glycine, respectively, with respect to antagonist specificity, reversal potential, and ionic permeability. The APV- and strychnine-sensitive currents also showed a time dependence similar to that of the currents elicited by NMDA and glycine. EC50 values could not be calculated, because the response did not saturate within the tested range of L-proline concentrations (0.3-50 mM). Estimates of relative potency were obtained, however, by comparison with responses elicited by selective agonists. The APV-sensitive, CNQX-sensitive, and strychnine-sensitive currents evoked by 10 mM L-proline were comparable in size to currents elicited by 15 microM NMDA, 5 microM kainate, and 30 microM glycine, respectively. L-Proline was found to elicit an increase in intracellular [Ca2+] that was dependent upon Ca2+ entry into the cell. These Ca2+ responses were enhanced by strychnine and partially antagonized by APV, CNQX, or Mg2+. Our results using dorsal horn neurons grown in culture indicate that L-proline is a weak agonist at strychnine-sensitive glycine receptors and at both NMDA and non-NMDA glutamate receptors. These observations should help in interpreting the confusing array of L-proline actions that have been described using more intact nervous system preparations. Furthermore, the ability of L-proline to stimulate Ca2+ entry after activation of excitatory amino acid receptors implicates L-proline as a potential endogenous excitotoxin.
Mol Pharmacol 1992 Apr
PMID:L-proline activates glutamate and glycine receptors in cultured rat dorsal horn neurons. 134 55

Whole-cell recordings from rat cortical neurons in dissociated cell culture were used to study the antagonism of glutamate receptors by several lipophilic benzazepine analogues of 2,5-dihydro-2,5-dioxo-3-hydroxy-1H-benzazepine (DDHB). DDHB and three substituted derivatives, 4-bromo-, 7-methyl-, and 8-methyl-DDHB, inhibited the activation of N-methyl-D-aspartate (NMDA) receptors at both the NMDA recognition site and the glycine allosteric site. In addition, all four compounds blocked the activation of non-NMDA receptors by kainate and L-glutamate. Antagonism by the four benzazepines was equivalent at holding potentials from -80 mV to +50 mV. Both the onset of and recovery from block of the agonist-gated currents were complete within seconds. Antagonist affinity was calculated from the displacement of steady state concentration-response curves for kainate, L-glutamate, glycine, and NMDA, based on the Gaddum-Schild relationship (dose ratio = 1 + [antagonist]/KB). The most potent blocker, 8-Me-DDHB, had an apparent dissociation constant (KB) of 470 nM at the glycine allosteric site and 27 microM at the NMDA recognition site. The apparent dissociation constant of 8-Me-DDHB for non-NMDA receptors was 6.4 microM when kainate was the agonist and 9.6 microM when L-glutamate was the agonist. Unsubstituted DDHB showed slightly higher affinity for the NMDA recognition site (KB = 16 microM) but was less potent than 8-Me-DDHB at the glycine allosteric site and at non-NMDA receptors (KB = 3 and 65 microM, respectively). At all three sites, the inhibitory actions of these benzazepine derivatives were consistent with a simple competitive mechanism of antagonism. In addition, the antagonist potency of the parent compound, DDHB, against kainate, NMDA, and glycine was equal to or greater than that of other bicyclic antagonists, including kynurenic acid, indole-2-carboxylic acid, and quinoxaline-2,3-dione. Substituted benzazepines represent a new class of glutamate receptor antagonists that show competitive action, significant potency at multiple sites, and a high degree of lipophilicity.
Mol Pharmacol 1992 Jun
PMID:Competitive antagonism of glutamate receptor channels by substituted benzazepines in cultured cortical neurons. 135 36


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