KAINIC ACID, AMPA, AND DIHYDROKAINIC ACID EFFECT ON UPTAKE AND EFFLUXOF D-[H-3]ASPARTIC ACID IN CEREBELLAR SLICES

In this study we show that the glutamate ionotropic agonist kainate (K A) stimulates the efflux of preloaded D-[H-3]aspartate (D-[3H]Asp) and inhibits the uptake of this amino acid in cerebellar slices. The effe ct of this agonist on the efflux of D-[H-3]Asp is sensitive to (i) 6-n itro-7-sulphamoylbenzo(f)quinoxaline-2-3-dione (NBQX), indicating the involvement of lpha-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-sensitiv e) KA/AMPA receptors are involved. In contrast, the effect on uptake i s NBQX- and TTX-insensitive indicating a direct interaction with gluta mate transporters. AMPA inhibited D-[H-3]Asp uptake and had no effect on D-[H-3]Asp efflux. In the same system, the uptake but not the efflu x of D-[H-3]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.