Kainic acid, AMPA, and dihydrokainic acid effect on uptake and efflux of D-[3H] aspartic acid in cerebellar slices.
In this study we show that the glutamate ionotropic agonist kainate (KA) stimulates the efflux of preloaded D-[3H]aspartate (D-[3H]Asp) and inhibits the uptake of this amino acid in cerebellar slices. The effect of this agonist on the efflux of D-[3H]Asp is sensitive to (i) 6-nitro-7-sulphamoylbenzo(f)quinoxaline-2-3-dione (NBQX), indicating the involvement of KA/(RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, and is (ii) partially tetrodotoxin (TTX)-sensitive, indicating that pre-(TTX-insensitive) and post-synaptic (TTX-sensitive) KA/AMPA receptors are involved. In contrast, the effect on uptake is NBQX- and TTX-insensitive indicating a direct interaction with glutamate transporters. AMPA inhibited D-[3H]Asp uptake and had no effect on D-[3H]Asp efflux. In the same system, the uptake but not the efflux of D-[3H]Asp was affected by dihydrokainate (DHK). The DHK-induced uptake inhibition occurred in the presence of TTX. NBQX inhibited DHK-induced effect at 5 mM but not at 1 mM DHK concentrations.
Bouazzaoui
M
M
Laboratoire de Neurobiologie Cellulaire, UPR 9009 CNRS, Centre de Neurochimie, Strasbourg, France.
Kannengieser
C
C
Procksch
O
O
Gombos
G
G
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D007700:Kinetics; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013779:Tetrodotoxin / Q000494:pharmacology; D014316:Tritium; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology*
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D014316:Tritium; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D001224:Aspartic Acid; D013779:Tetrodotoxin; C020889:dihydrokainic acid; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D007608:Kainic Acid