BIOMAT Database Logo BIOMAT Database Logo

Actions of D-cycloserine at the N-methyl-D-aspartate-associated glycine receptor site in vivo. 1991

M R Emmett, and S J Mick, and J A Cler, and T S Rao, and S Iyengar, and P L Wood
Searle Research and Development, Monsanto Company, St Louis, MO 63198.

The antibiotic, D-cycloserine has been shown to be a partial agonist at the N-methyl-D-aspartate (NMDA)-coupled, strychnine-insensitive glycine receptor by in vitro receptor binding. This partial agonism was further investigated in an in vivo system, by monitoring changes in levels of cyclic guanosine-monophosphate (cGMP), a well characterized second messenger response, mediated by the NMDA receptor complex, in the cerebellum of the mouse. Parenteral injections of D-cycloserine produced a biphasic dose-response curve which suggested partial agonism. In support of this contention, when intracerebellar injections were made together with D-serine, a glycine agonist, D-cycloserine attenuated the N-methyl-D-aspartate receptor-mediated increase in levels of cGMP. Likewise, systemic administration of D-cycloserine attenuated increases in cGMP induced by pentylenetetrazol. These data are relevant to the study of N-methyl-D-aspartate-mediated neurotransmission, since D-cycloserine is a parenterally bioavailable compound, with both agonist and depressant properties at the N-methyl-D-aspartate-associated glycine receptor.

UI MeSH Term Description Entries
D007279 Injections, Subcutaneous Forceful administration under the skin of liquid medication, nutrient, or other fluid through a hollow needle piercing the skin. Subcutaneous Injections,Injection, Subcutaneous,Subcutaneous Injection
D008297 Male Males
D002531 Cerebellum The part of brain that lies behind the BRAIN STEM in the posterior base of skull (CRANIAL FOSSA, POSTERIOR). It is also known as the "little brain" with convolutions similar to those of CEREBRAL CORTEX, inner white matter, and deep cerebellar nuclei. Its function is to coordinate voluntary movements, maintain balance, and learn motor skills. Cerebella,Corpus Cerebelli,Parencephalon,Cerebellums,Parencephalons
D003523 Cycloserine Antibiotic substance produced by Streptomyces garyphalus. R-4-Amino-3-isoxazolidinone,Seromycin
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
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
D006152 Cyclic GMP Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed) Guanosine Cyclic 3',5'-Monophosphate,Guanosine Cyclic 3,5 Monophosphate,Guanosine Cyclic Monophosphate,Guanosine Cyclic-3',5'-Monophosphate,3',5'-Monophosphate, Guanosine Cyclic,Cyclic 3',5'-Monophosphate, Guanosine,Cyclic Monophosphate, Guanosine,Cyclic-3',5'-Monophosphate, Guanosine,GMP, Cyclic,Guanosine Cyclic 3',5' Monophosphate,Monophosphate, Guanosine Cyclic
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
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus

Related Publications

M R Emmett, and S J Mick, and J A Cler, and T S Rao, and S Iyengar, and P L Wood
Glycine site-directed agonists reverse the actions of ethanol at the N-methyl-D-aspartate receptor.
December 1990, Molecular pharmacology,
M R Emmett, and S J Mick, and J A Cler, and T S Rao, and S Iyengar, and P L Wood
Pharmacological characteristics of cyclic homologues of glycine at the N-methyl-D-aspartate receptor-associated glycine site.
August 1990, Neuropharmacology,
M R Emmett, and S J Mick, and J A Cler, and T S Rao, and S Iyengar, and P L Wood
Divalent cations modulate N-methyl-D-aspartate receptor function at the glycine site.
September 1999, The Journal of pharmacology and experimental therapeutics,
M R Emmett, and S J Mick, and J A Cler, and T S Rao, and S Iyengar, and P L Wood
Genomic Triplication of the Glycine Decarboxylase Gene and N-Methyl-D-Aspartate Receptor Hypofunction: Improvement by Glycine and D-Cycloserine.
October 2019, Biological psychiatry,
M R Emmett, and S J Mick, and J A Cler, and T S Rao, and S Iyengar, and P L Wood
D-cycloserine: a ligand for the N-methyl-D-aspartate coupled glycine receptor has partial agonist characteristics.
March 1989, Neuroscience letters,
M R Emmett, and S J Mick, and J A Cler, and T S Rao, and S Iyengar, and P L Wood
Neurotoxicity associated with dual actions of homocysteine at the N-methyl-D-aspartate receptor.
May 1997, Proceedings of the National Academy of Sciences of the United States of America,
M R Emmett, and S J Mick, and J A Cler, and T S Rao, and S Iyengar, and P L Wood
Differential modulation of the associated glycine recognition site by competitive N-methyl-D-aspartate receptor antagonists.
June 1990, Molecular pharmacology,
M R Emmett, and S J Mick, and J A Cler, and T S Rao, and S Iyengar, and P L Wood
Competitive antagonism of glycine at the N-methyl-D-aspartate (NMDA) receptor.
January 1991, Biochemical pharmacology,
M R Emmett, and S J Mick, and J A Cler, and T S Rao, and S Iyengar, and P L Wood
Spermine enhances binding to the glycine site associated with the N-methyl-D-aspartate receptor complex.
December 1989, Molecular pharmacology,
M R Emmett, and S J Mick, and J A Cler, and T S Rao, and S Iyengar, and P L Wood
Activity of 5,7-dichlorokynurenic acid, a potent antagonist at the N-methyl-D-aspartate receptor-associated glycine binding site.
October 1990, Molecular pharmacology,
Copied contents to your clipboard!