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Abusive stimulation of excitatory amino acid receptors: a strategy to limit neurotoxicity
Author(s) -
Manev Hari,
Costa Erminio,
Wroblewski Jarda T.,
Guidotti Alessandro
Publication year - 1990
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.4.10.2165013
Subject(s) - glutamate receptor , neuroscience , excitatory postsynaptic potential , synapse , intracellular , receptor , stimulation , biology , inhibitory postsynaptic potential , neurotransmission , long term depression , chemistry , microbiology and biotechnology , pharmacology , ampa receptor , biochemistry
Glutamate is an important excitatory amino acid at many central nervous system synapses. After its release from presynaptic nerve terminals, glutamate transiently binds to specific neuronal membrane receptors, which transduce its signal by the generation of intracellular second messengers before being rapidly cleared from the synapse. However, during ischemia, the glutamate concentration at synapses surrounding the focal lesion can be increased for sustained periods of time, resulting in abusive stimulation of glutamate receptors that can eventually be neurotoxic. To develop drugs capable of selectively blocking the pathological effects of glutamate in neurons surrounding ischemic lesions while leaving the physiological actions of glutamate in nonlesioned areas of the brain unaffected, it is essential to delineate glutamate‐induced intracellular events that are specific to receptor abuse. This article describes the intracellular sequelae of physiological and pathological glutamate receptor activation and suggests potential targets for such receptor abuse‐dependent antagonists (RADAs).— M anev , H.; C osta , E.; W roblewski , J. T.; G uidotti , A. Abusive stimulation of excitatory amino acid receptors: a strategy to limit neurotoxicity: FASEB J. 4: 2789‐2797; 1990.