BIOMAT Database Logo BIOMAT Database Logo

N-methyl-D-aspartate- or glutamate-mediated toxicity in cultured rat cortical neurons is antagonized by FPL 15896AR. 1995

M A Black, and R Tremblay, and G Mealing, and R Ray, and J P Durkin, and J F Whitfield, and J Blosser, and P Morley
Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada.

The neuroprotective action of (S)-alpha-phenyl-2-pyridineethanamine dihydrochloride (FPL 15896AR), a novel noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, was examined in primary rat cortical neuronal cultures. Exposure of cortical cultures to NMDA (50 microM) or glutamate (50 microM) for 15 min resulted in the death of 85-95% of the neurons during the next 24 h. This neurotoxicity was completely eliminated by adding FPL 15896AR (50 microM) to the cultures during the time of NMDA or glutamate exposure. Neuroprotective concentrations of FPL 15896AR also inhibited other acute effects of NMDA. FPL 15896AR (50 microM) prevented the loss of membrane-associated protein kinase C activity that developed by 4 h after transient exposure to 50 microM NMDA or 50 microM glutamate. FPL 15896AR also reduced by approximately 35% the magnitude of NMDA-triggered increases in intracellular free Ca2+ concentration in the cortical cultures. These data indicate that NMDA-mediated toxicity in cultured cortical neurons can be blocked by the NMDA antagonist FPL 15896AR.

UI MeSH Term Description Entries
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D011493 Protein Kinase C An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters. Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D011725 Pyridines Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D002540 Cerebral Cortex The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions. Allocortex,Archipallium,Cortex Cerebri,Cortical Plate,Paleocortex,Periallocortex,Allocortices,Archipalliums,Cerebral Cortices,Cortex Cerebrus,Cortex, Cerebral,Cortical Plates,Paleocortices,Periallocortices,Plate, Cortical
D005971 Glutamates Derivatives of GLUTAMIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure. Glutamic Acid Derivatives,Glutamic Acids,Glutaminic Acids
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
D016202 N-Methylaspartate An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA). N-Methyl-D-aspartate,NMDA,N-Methyl-D-aspartic Acid,Acid, N-Methyl-D-aspartic,N Methyl D aspartate,N Methyl D aspartic Acid,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

Related Publications

M A Black, and R Tremblay, and G Mealing, and R Ray, and J P Durkin, and J F Whitfield, and J Blosser, and P Morley
Propofol protects cultured rat hippocampal neurons against N-methyl-D-aspartate receptor-mediated glutamate toxicity.
October 1994, Journal of neurosurgical anesthesiology,
M A Black, and R Tremblay, and G Mealing, and R Ray, and J P Durkin, and J F Whitfield, and J Blosser, and P Morley
Bifemelane protects cultured cortical neurons against N-methyl-D-aspartate receptor-mediated glutamate cytotoxicity.
March 1998, Japanese journal of pharmacology,
M A Black, and R Tremblay, and G Mealing, and R Ray, and J P Durkin, and J F Whitfield, and J Blosser, and P Morley
Mercury-induced toxicity of rat cortical neurons is mediated through N-Methyl-D-Aspartate receptors.
September 2012, Molecular brain,
M A Black, and R Tremblay, and G Mealing, and R Ray, and J P Durkin, and J F Whitfield, and J Blosser, and P Morley
Prostaglandin E2 protects cultured cortical neurons against N-methyl-D-aspartate receptor-mediated glutamate cytotoxicity.
November 1994, Brain research,
M A Black, and R Tremblay, and G Mealing, and R Ray, and J P Durkin, and J F Whitfield, and J Blosser, and P Morley
Temperature-dependent N-methyl-D-aspartate receptor-mediated cytotoxicity in cultured rat cortical neurons.
August 2007, Neuroscience letters,
M A Black, and R Tremblay, and G Mealing, and R Ray, and J P Durkin, and J F Whitfield, and J Blosser, and P Morley
Antagonism of N-methyl-D-aspartate-evoked currents in rat cortical cultures by ARL 15896AR.
April 1997, The Journal of pharmacology and experimental therapeutics,
M A Black, and R Tremblay, and G Mealing, and R Ray, and J P Durkin, and J F Whitfield, and J Blosser, and P Morley
Nicotine-induced protection of cultured cortical neurons against N-methyl-D-aspartate receptor-mediated glutamate cytotoxicity.
May 1994, Brain research,
M A Black, and R Tremblay, and G Mealing, and R Ray, and J P Durkin, and J F Whitfield, and J Blosser, and P Morley
Zinc toxicity on cultured cortical neurons: involvement of N-methyl-D-aspartate receptors.
June 1994, Neuroscience,
M A Black, and R Tremblay, and G Mealing, and R Ray, and J P Durkin, and J F Whitfield, and J Blosser, and P Morley
Mechanisms of cholecystokinin-induced protection of cultured cortical neurons against N-methyl-D-aspartate receptor-mediated glutamate cytotoxicity.
October 1992, Brain research,
M A Black, and R Tremblay, and G Mealing, and R Ray, and J P Durkin, and J F Whitfield, and J Blosser, and P Morley
Protective effect of donepezil in primary-cultured rat cortical neurons exposed to N-methyl-d-aspartate (NMDA) toxicity.
January 2006, European journal of pharmacology,
Copied contents to your clipboard!