Oxidative stress induced by glutamate receptor agonists.
The effect of various selective glutamate agonists upon the rate of generation of reactive oxygen species (ROS), was examined in an isolated synaptoneurosomal (microsac) fraction derived from rat cerebral cortex. The rates of ROS generation were determined by a fluorescent probe. Agonists specific for each of the three major glutamate inotropic receptor sites (NMDA, kainic acid, alpha-amino-3-hydroxy-5-methyl-4-isoxalolpropionic acid, AMPA), were able to enhance rates of ROS generation. The metabotropic glutamate agonist trans-1-aminocyclopentane-1,3-dicarboxylic acid, (ACPD), was inactive in this regard. Stimulation of ROS was most pronounced in the case of kainate. Such results could not be replicated by use of ion-channel active agents, veratridine and A23817. Pretreatment with the kainate antagonist, 6-cyano-7-quinoxaline-2,3-dione (CNQX), was not able to block the kainate-induced elevation of ROS. Domoic acid, a kainate agonist, also enhanced microsac ROS generation. Neurological damage may result from generation of excess free radicals, and this may be effected by glutamate agonists acting by means independent of their ionotropic properties.
Bondy
S C
SC
Department of Community and Environmental Medicine, University of California, Irvine 92717.
Lee
D K
DK
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists; D005609:Free Radicals; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000502:physiology; D019335:Nitroarginine; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D017382:Reactive Oxygen Species / Q000378:metabolism; D017470:Receptors, Glutamate / Q000187:drug effects*; D013312:Stress, Physiological / Q000139:chemically induced* / Q000378:metabolism; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D005609:Free Radicals; D017382:Reactive Oxygen Species; D017470:Receptors, Glutamate; D019335:Nitroarginine; D001120:Arginine; D007608:Kainic Acid