Effect of excitatory amino acid analogues on the release of D-[3H]aspartate from chick retina.

There is good evidence to suggest that L-glutamate (L-Glu) and/or L-aspartate (L-Asp) might function as excitatory neurotransmitters in the vertebrate retina. Postsynaptic receptors for these compounds have been identified in both plexiform layers by means of physiological and biochemical techniques. However, the presence of excitatory amino acid receptors which could regulate the release of these compounds has not previously been demonstrated. We have now shown that the K+-stimulated, Ca2+-dependent release of [3H]D-aspartate from superfused chick retina is inhibited by L-Glu, N-methyl-D-aspartate (NMDA), kainate (KA) and several other neuroactive analogues. While alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and (+/-)2-amino-5-phosphonovaleric acid both exhibited agonist activity when tested alone, the former substance reversed the inhibition observed with L-Glu and KA whereas the latter effectively antagonized the NMDA-induced inhibition of release, possibly acting as partial agonists. The results demonstrate an interaction of NMDA and AMPA with KA probably at receptors in the chick retina that are involved in the regulation of glutamate/aspartate release.