Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Br J Pharmacol
2003 Nov 01;1405:839-46. doi: 10.1038/sj.bjp.0705509.
Show Gene links
Show Anatomy links
WAY-855 (3-amino-tricyclo[2.2.1.02.6]heptane-1,3-dicarboxylic acid): a novel, EAAT2-preferring, nonsubstrate inhibitor of high-affinity glutamate uptake.
Dunlop J
,
Eliasof S
,
Stack G
,
McIlvain HB
,
Greenfield A
,
Kowal D
,
Petroski R
,
Carrick T
.
???displayArticle.abstract???
The pharmacological profile of a novel glutamate transport inhibitor, WAY-855 (3-amino-tricyclo[2.2.1.0(2.6)]heptane-1,3-dicarboxylic acid), on the activity of the human forebrain glutamate transporters EAAT1, EAAT2 and EAAT3 expressed in stable mammalian cell lines and in Xenopus laevis oocytes is presented. WAY-855 inhibited glutamate uptake mediated by all three subtypes in a concentration-dependent manner, with preferential inhibition of the CNS-predominant EAAT2 subtype in both cells and oocytes. IC50 values for EAAT2 and EAAT3 inhibition in cells were 2.2 and 24.5 microM, respectively, while EAAT1 activity was inhibited by 50% at 100 microM (IC50 values determined in oocytes were 1.3 microM (EAAT2), 52.5 microM (EAAT3) and 125.9 microM (EAAT1)). Application of WAY-855 to EAAT-expressing oocytes failed to induce a transporter current, and the compound failed to exchange with accumulated [3H]d-aspartate in synaptosomes consistent with a nonsubstrate inhibitor. WAY-855 inhibited d-aspartate uptake into cortical synaptosomes by a competitive mechanism, and with similar potency to that observed for the cloned EAAT2. WAY-855 failed to agonise or antagonise ionotropic glutamate receptors in cultured hippocampal neurones, or the human metabotropic glutamate receptor subtype 4 expressed in a stable cell line. WAY-855 represents a novel structure in glutamate transporter pharmacology, and exploration of this structure might provide insights into the discrimination between EAAT2 and other EAAT subtypes.
Arriza,
Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex.
1994, Pubmed,
Xenbase
Arriza,
Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex.
1994,
Pubmed
,
Xenbase
Arriza,
Excitatory amino acid transporter 5, a retinal glutamate transporter coupled to a chloride conductance.
1997,
Pubmed
,
Xenbase
Barnard,
Ionotropic glutamate receptors: new types and new concepts.
1997,
Pubmed
Bergles,
Synaptic activation of glutamate transporters in hippocampal astrocytes.
1997,
Pubmed
Bridges,
Conformationally defined neurotransmitter analogues. Selective inhibition of glutamate uptake by one pyrrolidine-2,4-dicarboxylate diastereomer.
1991,
Pubmed
Bridges,
A pharmacological review of competitive inhibitors and substrates of high-affinity, sodium-dependent glutamate transport in the central nervous system.
1999,
Pubmed
Conn,
Pharmacology and functions of metabotropic glutamate receptors.
1997,
Pubmed
Danbolt,
Glutamate uptake.
2001,
Pubmed
Dunlop,
Substrate exchange properties of the high-affinity glutamate transporter EAAT2.
2001,
Pubmed
Dunlop,
Inducible expression and pharmacology of the human excitatory amino acid transporter 2 subtype of L-glutamate transporter.
1999,
Pubmed
Fairman,
An excitatory amino-acid transporter with properties of a ligand-gated chloride channel.
1995,
Pubmed
,
Xenbase
Fletcher,
Inhibition of high affinity L-glutamic acid uptake into rat cortical synaptosomes by the conformationally restricted analogue of glutamic acid, cis-1-aminocyclobutane-1,3-dicarboxylic acid.
1991,
Pubmed
Griffiths,
L-trans-pyrrolidine-2,4-dicarboxylate and cis-1-aminocyclobutane-1,3-dicarboxylate behave as transportable, competitive inhibitors of the high-affinity glutamate transporters.
1994,
Pubmed
Kanai,
Primary structure and functional characterization of a high-affinity glutamate transporter.
1992,
Pubmed
,
Xenbase
Koch,
Differentiation of substrate and nonsubstrate inhibitors of the high-affinity, sodium-dependent glutamate transporters.
1999,
Pubmed
,
Xenbase
Kowal,
A [35S]GTPgammaS binding assessment of metabotropic glutamate receptor standards in Chinese hamster ovary cell lines expressing the human metabotropic receptor subtypes 2 and 4.
1998,
Pubmed
Nakamura,
(2S,3S,4R)-2-(carboxycyclopropyl)glycine, a potent and competitive inhibitor of both glial and neuronal uptake of glutamate.
1993,
Pubmed
Otis,
Anion currents and predicted glutamate flux through a neuronal glutamate transporter.
1998,
Pubmed
Pines,
Cloning and expression of a rat brain L-glutamate transporter.
1992,
Pubmed
Robinson,
Pharmacologically distinct sodium-dependent L-[3H]glutamate transport processes in rat brain.
1991,
Pubmed
Rothstein,
Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate.
1996,
Pubmed
Schoepp,
Pharmacological agents acting at subtypes of metabotropic glutamate receptors.
1999,
Pubmed
Shigeri,
Effects of threo-beta-hydroxyaspartate derivatives on excitatory amino acid transporters (EAAT4 and EAAT5).
2001,
Pubmed
,
Xenbase
Shimamoto,
DL-threo-beta-benzyloxyaspartate, a potent blocker of excitatory amino acid transporters.
1998,
Pubmed
,
Xenbase
Storck,
Structure, expression, and functional analysis of a Na(+)-dependent glutamate/aspartate transporter from rat brain.
1992,
Pubmed
,
Xenbase
Tan,
Expression of the GLT-1 subtype of Na+-dependent glutamate transporter: pharmacological characterization and lack of regulation by protein kinase C.
1999,
Pubmed
Tanaka,
Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1.
1997,
Pubmed
Vandenberg,
Contrasting modes of action of methylglutamate derivatives on the excitatory amino acid transporters, EAAT1 and EAAT2.
1997,
Pubmed
,
Xenbase
Wang,
Dihydrokainate-sensitive neuronal glutamate transport is required for protection of rat cortical neurons in culture against synaptically released glutamate.
1998,
Pubmed
Ziff,
Recent excitement in the ionotropic glutamate receptor field.
1999,
Pubmed
