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Identification of a subunit-specific antagonist of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate/kainate receptor channels.
Keller BU
,
Blaschke M
,
Rivosecchi R
,
Hollmann M
,
Heinemann SF
,
Konnerth A
.
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Excitatory synaptic transmission in the mammalian central nervous system is mediated predominantly by glutamate receptor (GluR) channels of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate/kainate (AMPA/KA) receptor type. A major improvement in our understanding of glutamatergic synaptic transmission has been achieved after the identification of quinoxalinediones (e.g., 6-cyano-7-nitroquinoxaline-2,3-dione) as specific antagonists of AMPA/KA receptors. In addition to their effects on neurons, quinoxalinediones were also shown to block glutamate-induced responses mediated by recombinant AMPA/KA receptor channels expressed in heterologous systems, irrespective of their particular subunit composition. Here we report the identification of an AMPA/KA receptor antagonist that selectively blocks a subset of AMPA/KA receptors. We found that Evans blue, a biphenyl derivative of naphthalene disulfonic acid, blocks at low concentrations (IC50 = 355 nM for the subunit combination GluR1,2) KA-mediated responses of the subunits GluR1, GluR1,2, GluR1,3, and GluR2,3 expressed in Xenopus oocytes but not responses of GluR3 or GluR6. The blocking action of Evans blue was partially reversible and did not compete with KA for the agonist binding site. These findings suggest not only that Evans blue is a potent tool for elucidating the functional role of specific AMPA/KA receptor subtypes for excitatory synaptic transmission but also that it may also represent a powerful starting point for clinically useful drugs that are able to reduce the excitatory drive in specific neuronal populations of the central nervous system.
Boulter,
Molecular cloning and functional expression of glutamate receptor subunit genes.
1990, Pubmed,
Xenbase
Boulter,
Molecular cloning and functional expression of glutamate receptor subunit genes.
1990,
Pubmed
,
Xenbase
Burnashev,
Divalent ion permeability of AMPA receptor channels is dominated by the edited form of a single subunit.
1992,
Pubmed
Dewar,
Selective reduction of quisqualate (AMPA) receptors in Alzheimer cerebellum.
1990,
Pubmed
Difazio,
Glutamate receptors in the substantia nigra of Parkinson's disease brains.
1992,
Pubmed
Dingledine,
Excitatory amino acid receptors in epilepsy.
1990,
Pubmed
Egebjerg,
Cloning of a cDNA for a glutamate receptor subunit activated by kainate but not AMPA.
1991,
Pubmed
,
Xenbase
Harrison,
Distribution of a kainate/AMPA receptor mRNA in normal and Alzheimer brain.
1990,
Pubmed
Hollmann,
Ca2+ permeability of KA-AMPA--gated glutamate receptor channels depends on subunit composition.
1991,
Pubmed
,
Xenbase
Hollmann,
Cloning by functional expression of a member of the glutamate receptor family.
1989,
Pubmed
,
Xenbase
Honoré,
Quinoxalinediones: potent competitive non-NMDA glutamate receptor antagonists.
1988,
Pubmed
Hosford,
Increased AMPA-sensitive quisqualate receptor binding and reduced NMDA receptor binding in epileptic human hippocampus.
1991,
Pubmed
Hume,
Identification of a site in glutamate receptor subunits that controls calcium permeability.
1991,
Pubmed
,
Xenbase
Keinänen,
A family of AMPA-selective glutamate receptors.
1990,
Pubmed
Keller,
Calcium influx through subunits GluR1/GluR3 of kainate/AMPA receptor channels is regulated by cAMP dependent protein kinase.
1992,
Pubmed
,
Xenbase
Keller,
Patch clamp analysis of excitatory synaptic currents in granule cells of rat hippocampus.
1991,
Pubmed
Klockgether,
The AMPA receptor antagonist NBQX has antiparkinsonian effects in monoamine-depleted rats and MPTP-treated monkeys.
1991,
Pubmed
Lessmann,
Evans blue reduces macroscopic desensitization of non-NMDA receptor mediated currents and prolongs excitatory postsynaptic currents in cultured rat thalamic neurons.
1992,
Pubmed
Llano,
Synaptic- and agonist-induced excitatory currents of Purkinje cells in rat cerebellar slices.
1991,
Pubmed
Löschmann,
Synergism of the AMPA-antagonist NBQX and the NMDA-antagonist CPP with L-dopa in models of Parkinson's disease.
1991,
Pubmed
Mayer,
The physiology of excitatory amino acids in the vertebrate central nervous system.
1987,
Pubmed
McDonald,
Altered excitatory and inhibitory amino acid receptor binding in hippocampus of patients with temporal lobe epilepsy.
1991,
Pubmed
Methfessel,
Patch clamp measurements on Xenopus laevis oocytes: currents through endogenous channels and implanted acetylcholine receptor and sodium channels.
1986,
Pubmed
,
Xenbase
Monaghan,
The excitatory amino acid receptors: their classes, pharmacology, and distinct properties in the function of the central nervous system.
1989,
Pubmed
Nakanishi,
A family of glutamate receptor genes: evidence for the formation of heteromultimeric receptors with distinct channel properties.
1990,
Pubmed
Pedder,
Quisqualate receptors in epileptic fowl: the absence of coupling between quisqualate and N-methyl-D-aspartate receptors.
1990,
Pubmed
Pellegrini-Giampietro,
Differential expression of three glutamate receptor genes in developing rat brain: an in situ hybridization study.
1991,
Pubmed
Schneggenburger,
Excitatory and inhibitory synaptic currents and receptors in rat medial septal neurones.
1992,
Pubmed
Verdoorn,
Structural determinants of ion flow through recombinant glutamate receptor channels.
1991,
Pubmed
