[Excitatory amino acids and neuronal death].
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.
Shinozaki
H
H
Department of Pharmacology, Tokyo Metropolitan Institute of Medical Science.
D000818:Animals; D016923:Cell Death; D002490:Central Nervous System / Q000473:pathology / Q000503:physiopathology; D003521:Cyclopropanes / Q000494:pharmacology; D018846:Excitatory Amino Acids / Q000633:toxicity; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D051381:Rats; D017470:Receptors, Glutamate / Q000378:metabolism / Q000502:physiology
D003521:Cyclopropanes; D018846:Excitatory Amino Acids; D017470:Receptors, Glutamate; C082313:2-(2,3-dicarboxycyclopropyl)glycine; D005998:Glycine