Effects of D-aspartate on excitatory amino acid-induced release of [3H]GABA from goldfish retina.
The rate of release of [3H]GABA from isolated intact goldfish retinas was studied. Release of [3H]GABA is markedly stimulated by the inclusion in the incubation medium of the photoreceptor neurotransmitter candidates L-glutamate (L-Glu) and L-aspartate (L-Asp), and the glutamate analogs, kainate and quisqualate. At micromolar concentrations, kainate and quisqualate are effective releasers of [3H]GABA, whereas millimolar concentrations of L-Glu and L-Asp are required to release comparable amounts of [3H]GABA. The D-isomers of aspartate (D-Asp) and glutamate (D-Glu) are able to release [3H]GABA, but only when applied at high concentrations (3-30 mM). In the presence of 5 mM D-Asp, the effect of L-Glu in releasing [3H]GABA was markedly potentiated. This dose-response curve of L-Glu was shifted to the left in the presence of D-Asp, although the maximal amount of release was unchanged. D-Asp at 5 mM only slightly increased the GABA release induced by quisqualate, and it did not increase the GABA release induced by kainate. Finally, low concentrations of L-Asp were potentiated by D-Asp, but higher concentrations of L-Asp (3-10 mM) were clearly inhibited by this agent. This biphasic effect of D-Asp on L-Asp-induced release of [3H]GABA is a possible explanation for previously conflicting reports of D-Asp's effect on L-Asp action. Our data suggest that D-Asp has both pre- and postsynaptic sites of action.
Cha
J H
JH
O'Brien
D R
DR
Dowling
J E
JE
D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D006054:Goldfish; D007608:Kainic Acid / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D016318:Quisqualic Acid; D012160:Retina / Q000378:metabolism*; D014316:Tritium / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000596:Amino Acids; D005971:Glutamates; D010069:Oxadiazoles; D014316:Tritium; D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D016318:Quisqualic Acid; D007608:Kainic Acid