Differentiation of L-aspartate and L-glutamate high-affinity binding sites in a protein fraction isolated from rat cerebral cortex

Abstract

THE possibility that L-glutamate and L-aspartate are excitatory transmitters in the CNS is supported by neurochemical and neurophysiological evidence¹. The problems of identifying particular synapses that are excited by one or the other of these dicarboxylic amino acids, and distinguishing between the two receptors are, however, more difficult. At the recent International Meeting of Neurochemistry (September 1975) Graham summarised some of the evidence favouring distinct functions for the two amino acids, concentrating on the possible transmitter role of L-aspartate. For example, a higher content of this amino acid is found in the ventral than in the dorsal grey matter of the spinal cord², aortic occlusion leads to loss of aspartate content and degeneration of small neurones³, reduction in aspartate content is seen in the spinal cord after section of dorsal roots⁴ and in the olfactory cortex after olfactory bulbectomy⁵, which also decreases glutamate. Renshaw cells are slightly more sensitive to the ionotophoretic administration of L-aspartate while the reverse is true of interneurones of the dorsal spinal horn⁶. It is possible that L-glutamate and L-aspartate, being flexible molecules, fold or unfold and could interact with either receptor and McCulloch et al.⁷ accordingly used kainate, a conformational restricted analogue of glutamic acid, which would be unlikely to fold to occupy the aspartate receptor, and N-methyl-D-aspartate, which would be too small to interact with the glutamate receptor (Fig. 1). The difference in sensitivity between the two groups of neurones to these agonists was much greater: the Renshaw cells were much more sensitive to N-methyl-D-aspartate and the dorsal interneurones to kainate⁷.