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Proc Natl Acad Sci U S A
1998 Jul 21;9515:8969-74. doi: 10.1073/pnas.95.15.8969.
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Direct effects of metabotropic glutamate receptor compounds on native and recombinant N-methyl-D-aspartate receptors.
Contractor A
,
Gereau RW
,
Green T
,
Heinemann SF
.
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The actions of glutamate in the central nervous system are mediated through interaction with fast activating ionotropic receptors and G protein-coupled metabotropic glutamate receptors (mGluRs). Studies of these receptors have relied on the availability of agonists and antagonists selective for each receptor class. Compounds that were thought to be selective for mGluRs have been extensively used to study the role of these receptors in the brain. Their use has implicated mGluRs in a wide range of physiological and pathological processes including the modulation of N-methyl-D-aspartate (NMDA) receptors and NMDA receptor-dependent processes. We report that some of the most commonly used mGluR compounds act as antagonists on NMDA receptors at concentrations commonly used to activate or block mGluRs. In addition, several of the drugs also act as agonists at higher concentrations due at least in part to high levels of contaminant amino acids. Our results indicate that caution should be used when using these drugs to study the roles of mGluRs in various NMDA-dependent processes. The antagonist effects were dependent on the concentration of the NMDA receptor coagonists, preventing reappraisal of previously published work.
Ambrosini,
Metabotropic glutamate receptors negatively coupled to adenylate cyclase inhibit N-methyl-D-aspartate receptor activity and prevent neurotoxicity in mesencephalic neurons in vitro.
1995, Pubmed
Ambrosini,
Metabotropic glutamate receptors negatively coupled to adenylate cyclase inhibit N-methyl-D-aspartate receptor activity and prevent neurotoxicity in mesencephalic neurons in vitro.
1995,
Pubmed
Bashir,
Induction of LTP in the hippocampus needs synaptic activation of glutamate metabotropic receptors.
1993,
Pubmed
Bashir,
An investigation of depotentiation of long-term potentiation in the CA1 region of the hippocampus.
1994,
Pubmed
Bekkers,
Excitatory and inhibitory autaptic currents in isolated hippocampal neurons maintained in cell culture.
1991,
Pubmed
Breakwell,
(+)-MCPG blocks induction of LTP in CA1 of rat hippocampus via agonist action at an mGluR group II receptor.
1998,
Pubmed
Brown,
(RS)-alpha-methyl-4-carboxyphenylglycine (MCPG) does not block theta burst-induced long-term potentiation in area CA1 of rat hippocampal slices.
1994,
Pubmed
Buisson,
DCG-IV selectively attenuates rapidly triggered NMDA-induced neurotoxicity in cortical neurons.
1996,
Pubmed
Cheng,
Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction.
1973,
Pubmed
Chinestra,
(RS)-alpha-methyl-4-carboxyphenylglycine neither prevents induction of LTP nor antagonizes metabotropic glutamate receptors in CA1 hippocampal neurons.
1993,
Pubmed
Conn,
Pharmacology and functions of metabotropic glutamate receptors.
1997,
Pubmed
Evans,
The effects of a series of omega-phosphonic alpha-carboxylic amino acids on electrically evoked and excitant amino acid-induced responses in isolated spinal cord preparations.
1982,
Pubmed
Gereau,
Role of protein kinase C phosphorylation in rapid desensitization of metabotropic glutamate receptor 5.
1998,
Pubmed
,
Xenbase
Hollmann,
Zinc potentiates agonist-induced currents at certain splice variants of the NMDA receptor.
1993,
Pubmed
,
Xenbase
Höfner,
Characterisation of the binding of [3H]MDL 105,519, a radiolabelled antagonist for the N-methyl-D-aspartate-associated glycine site, to pig cortical brain membranes.
1997,
Pubmed
Izumi,
Developmental changes in the effects of metabotropic glutamate receptor antagonists on CA1 long-term potentiation in rat hippocampal slices.
1994,
Pubmed
Knöpfel,
Metabotropic glutamate receptors: novel targets for drug development.
1995,
Pubmed
Koh,
Activation of the metabotropic glutamate receptor attenuates N-methyl-D-aspartate neurotoxicity in cortical cultures.
1991,
Pubmed
Kutsuwada,
Molecular diversity of the NMDA receptor channel.
1992,
Pubmed
,
Xenbase
Laurie,
Ligand affinities at recombinant N-methyl-D-aspartate receptors depend on subunit composition.
1994,
Pubmed
Little,
Metabotropic glutamate receptor antagonist, (R,S)-alpha-methyl-4-carboxyphenyglycine, blocks two distinct forms of long-term potentiation in area CA1 of rat hippocampus.
1995,
Pubmed
Manzoni,
MCPG antagonizes metabotropic glutamate receptors but not long-term potentiation in the hippocampus.
1994,
Pubmed
Nakanishi,
Metabotropic glutamate receptors: synaptic transmission, modulation, and plasticity.
1994,
Pubmed
Nicoletti,
Metabotropic glutamate receptors: a new target for the therapy of neurodegenerative disorders?
1996,
Pubmed
Pin,
The metabotropic glutamate receptors: structure and functions.
1995,
Pubmed
Pizzi,
Metabotropic and ionotropic transducers of glutamate signal inversely control cytoplasmic Ca2+ concentration and excitotoxicity in cultured cerebellar granule cells: pivotal role of protein kinase C.
1996,
Pubmed
Richter-Levin,
Activation of metabotropic glutamate receptors is necessary for long-term potentiation in the dentate gyrus and for spatial learning.
1994,
Pubmed
Riedel,
Inhibition of long-term potentiation in the dentate gyrus of freely moving rats by the metabotropic glutamate receptor antagonist MCPG.
1995,
Pubmed
Riedel,
Function of metabotropic glutamate receptors in learning and memory.
1996,
Pubmed
Selig,
Reexamination of the effects of MCPG on hippocampal LTP, LTD, and depotentiation.
1995,
Pubmed
Sergueeva,
An antagonist of glutamate metabotropic receptors, (RS)-alpha-methyl-4-carboxyphenylglycine, prevents the LTP-related increase in postsynaptic AMPA sensitivity in hippocampal slices.
1993,
Pubmed
Sladeczek,
Glutamate stimulates inositol phosphate formation in striatal neurones.
,
Pubmed
Stern,
Single-channel conductances of NMDA receptors expressed from cloned cDNAs: comparison with native receptors.
1992,
Pubmed
,
Xenbase
Swanson,
Identification of amino acid residues that control functional behavior in GluR5 and GluR6 kainate receptors.
1997,
Pubmed
Thomas,
The molecular switch hypothesis fails to explain the inconsistent effects of the metabotropic glutamate receptor antagonist MCPG on long-term potentiation.
1995,
Pubmed
Wang,
(RS)-alpha-Methyl-4-carboxyphenylglycine inhibits long-term potentiation only following the application of low frequency stimulation in the rat dentate gyrus in vitro.
1995,
Pubmed