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.