Glycine reverses 7-chlorokynurenic acid-induced inhibition of [3H]MK-801 binding. 1989

R Sircar, and M J Frusciante, and D C Javitt, and S R Zukin
Department of Psychiatry, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY 10461.

7-Chlorokynurenic acid (7-Cl KYNA) has been reported to attenuate N-methyl-D-aspartate (NMDA) receptor functioning by a potent and selective inhibitory action mediated at the strychnine-insensitive glycine recognition site of the NMDA complex. Here we report that 7-Cl KYNA dose-dependently inhibits [3H]MK-801 binding to the PCP receptor, and that this effect is reversed by addition of glycine. Since [3H]MK-801 binding is a measure of channel activation, our results are consistent with the hypotheses that 7-Cl KYNA exerts its NMDA receptor antagonism by acting at the glycine site, and that activation of the glycine site is required for NMDA channel activity to occur.

UI MeSH Term Description Entries
D007736 Kynurenic Acid A broad-spectrum excitatory amino acid antagonist used as a research tool. Kynurenate,Acid, Kynurenic
D008297 Male Males
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D003986 Dibenzocycloheptenes A family of tricyclic hydrocarbons whose members include many of the commonly used tricyclic antidepressants (ANTIDEPRESSIVE AGENTS, TRICYCLIC).
D005998 Glycine A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. Aminoacetic Acid,Glycine, Monopotassium Salt,Glycine Carbonate (1:1), Monosodium Salt,Glycine Carbonate (2:1), Monolithium Salt,Glycine Carbonate (2:1), Monopotassium Salt,Glycine Carbonate (2:1), Monosodium Salt,Glycine Hydrochloride,Glycine Hydrochloride (2:1),Glycine Phosphate,Glycine Phosphate (1:1),Glycine Sulfate (3:1),Glycine, Calcium Salt,Glycine, Calcium Salt (2:1),Glycine, Cobalt Salt,Glycine, Copper Salt,Glycine, Monoammonium Salt,Glycine, Monosodium Salt,Glycine, Sodium Hydrogen Carbonate,Acid, Aminoacetic,Calcium Salt Glycine,Cobalt Salt Glycine,Copper Salt Glycine,Hydrochloride, Glycine,Monoammonium Salt Glycine,Monopotassium Salt Glycine,Monosodium Salt Glycine,Phosphate, Glycine,Salt Glycine, Monoammonium,Salt Glycine, Monopotassium,Salt Glycine, Monosodium
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D016194 Receptors, N-Methyl-D-Aspartate A class of ionotropic glutamate receptors characterized by affinity for N-methyl-D-aspartate. NMDA receptors have an allosteric binding site for glycine which must be occupied for the channel to open efficiently and a site within the channel itself to which magnesium ions bind in a voltage-dependent manner. The positive voltage dependence of channel conductance and the high permeability of the conducting channel to calcium ions (as well as to monovalent cations) are important in excitotoxicity and neuronal plasticity. N-Methyl-D-Aspartate Receptor,N-Methyl-D-Aspartate Receptors,NMDA Receptor,NMDA Receptor-Ionophore Complex,NMDA Receptors,Receptors, NMDA,N-Methylaspartate Receptors,Receptors, N-Methylaspartate,N Methyl D Aspartate Receptor,N Methyl D Aspartate Receptors,N Methylaspartate Receptors,NMDA Receptor Ionophore Complex,Receptor, N-Methyl-D-Aspartate,Receptor, NMDA,Receptors, N Methyl D Aspartate,Receptors, N Methylaspartate
D016291 Dizocilpine Maleate A potent noncompetitive antagonist of the NMDA receptor (RECEPTORS, N-METHYL-D-ASPARTATE) used mainly as a research tool. The drug has been considered for the wide variety of neurodegenerative conditions or disorders in which NMDA receptors may play an important role. Its use has been primarily limited to animal and tissue experiments because of its psychotropic effects. Dizocilpine,MK-801,MK 801,MK801
D017478 Receptors, Phencyclidine Specific sites or molecular structures on cell membranes or in cells with which phencyclidine reacts or to which it binds to elicit the specific response of the cell to phencyclidine. Studies have demonstrated the presence of multiple receptor sites for PCP. These are the PCP/sigma site, which binds both PCP and psychotomimetic opiates but not certain antipsychotics, and the PCP site, which selectively binds PCP analogs. PCP Receptors,Phencyclidine Receptors,Receptors, PCP,PCP Receptor,Phencylidine Receptor,Receptor, PCP,Receptor, Phencylidine
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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