[Excitatory amino acids and neuronal death]. 1995

H Shinozaki
Department of Pharmacology, Tokyo Metropolitan Institute of Medical Science.

Glutamic acid has been believed to be an excitatory transmitter in the mammalian central nervous system (CNS), and has been implicated in the pathogenesis of neuronal damage in the mammalian CNS. There are two major classes of glutamate receptors, ionotropic (iGluR) and metabotropic glutamate receptors (mGluR). Participation of iGluRs in glutamate mediated neurotoxicity has been well documented. However, much less is known about participation of mGluRs than the case for iGluRs. The physiological roles of mGluRs have been believed to regulate transmitter release and to modulate the function of iGluRs through activating various intracellular second messenger system. Recently we have discovered several potent agonists for mGluRs which would provide additional information about glutamate mediated neurotoxicity. DCG-IV, one of the most potent mGluR agonists, alleviated kainate-induced limbic motor seizures in extremely low doses in the rat, but the dose response curves showed a bell typed one. DCG-IV also demonstrated severe sedative condition and markedly prolonged the sleeping time in halothane anesthesia. DCG-IV depressed the duration of after-discharges and the seizures evoked by electrical stimulation in the amygdala kindling rat. DCG-IV significantly decreased in number of kainate-induced degenerated neurons in the area of hippocampal CA1, amygdala and septum when DCG-IV was continuously applied into the ventricule. In conclusion, activation of mGluRs leads the alleviation of neuron damage induced by iGluR agonists.

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
D002490 Central Nervous System The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. Cerebrospinal Axis,Axi, Cerebrospinal,Axis, Cerebrospinal,Central Nervous Systems,Cerebrospinal Axi,Nervous System, Central,Nervous Systems, Central,Systems, Central Nervous
D003521 Cyclopropanes Three-carbon cycloparaffin cyclopropane (the structural formula (CH2)3) and its derivatives.
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
D016923 Cell Death The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. Death, Cell
D017470 Receptors, Glutamate Cell-surface proteins that bind glutamate and trigger changes which influence the behavior of cells. Glutamate receptors include ionotropic receptors (AMPA, kainate, and N-methyl-D-aspartate receptors), which directly control ion channels, and metabotropic receptors which act through second messenger systems. Glutamate receptors are the most common mediators of fast excitatory synaptic transmission in the central nervous system. They have also been implicated in the mechanisms of memory and of many diseases. Excitatory Amino Acid Receptors,Glutamate Receptors,Receptors, Excitatory Amino Acid,Excitatory Amino Acid Receptor,Glutamate Receptor,Receptor, Glutamate
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
D018846 Excitatory Amino Acids Endogenous amino acids released by neurons as excitatory neurotransmitters. Glutamic acid is the most common excitatory neurotransmitter in the brain. Aspartic acid has been regarded as an excitatory transmitter for many years, but the extent of its role as a transmitter is unclear. Amino Acids, Excitatory,Excitatory Amino Acid,Acid, Excitatory Amino,Acids, Excitatory Amino,Amino Acid, Excitatory

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