title: Ionotropic glutamate receptors are involved in malondialdehyde production in anesthetized rat brain cortex: a microdialysis study.
abstract: Elevated extracellular glutamate levels can increase malondialdehyde production in the brains of anesthetized rats. Thus, we investigated whether ionotropic glutamate receptors are involved in glutamate-induced malondialdehyde production. A microdialysis probe was implanted in the brain cortex of anesthetized rats. The malondialdehyde level in microdialysates was analyzed using an HPLC system. Three different ionotropic glutamate receptor agonists were used. At a concentration of 1.5 mM alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid hydrobromide (AMPA, a selective AMPA receptor agonist) induced a dramatic increase in extracellular malondialdehyde production (as much as 14-fold relative to the basal value). N-Methyl-D-aspartic acid (NMDA, a selective NMDA receptor agonist) also induced an increase in extracellular malondialdehyde production; however, the increase was not as much as that observed in the perfusion of AMPA receptor agonist. Kainic acid (a selective kainate receptor agonist) did not significantly increase malondialdehyde production. When co-perfused with L-trans-pyrrolidine-2,4-dicarboxylate (PDC; 31.4 mM), a glutamate uptake transport inhibitor that can increase the extracellular glutamate levels, AMPA receptor antagonist [1-(4-aminophenyl)4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine hydrochloride, 1.0 mM] can significantly reduce PDC-induced malondialdehyde production. Although NMDA receptor antagonist [(5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate, MK801] also can decrease the PDC-induced malondialdehyde production, it was not as effective as the AMPA receptor antagonist. These results suggest that ionotropic receptors are involved in the glutamate-induced increase in malondialdehdye production. Specifically, AMPA receptor seems to be predominant in the glutamate-induced malondialdehdye production in anesthetized rat brain cortex.
authors.affiliation: Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan, ROC. cyang@ncnu.edu.tw
authors.forename: Chung-Shi
authors.initials: CS
authors.lastname: Yang
authors.forename: Pi-Ju
authors.initials: PJ
authors.lastname: Tsai
authors.forename: Wen-Ying
authors.initials: WY
authors.lastname: Chen
authors.forename: Jon-Son
authors.initials: JS
authors.lastname: Kuo
mesh_terms: D000758:Anesthesia; D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003998:Dicarboxylic Acids / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007608:Kainic Acid / Q000494:pharmacology; D008315:Malondialdehyde / Q000378:metabolism*; D010477:Perfusion; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017470:Receptors, Glutamate / Q000737:chemistry* / Q000378:metabolism; D013997:Time Factors; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
chemical_list: D003998:Dicarboxylic Acids; D018690:Excitatory Amino Acid Agonists; D011759:Pyrrolidines; D017470:Receptors, Glutamate; D008315:Malondialdehyde; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C083486:pyrrolidine-2,4-dicarboxylic acid; D007608:Kainic Acid