D-α-Aminoadipate as a selective antagonist of amino acid-induced and synaptic excitation of mammalian spinal neurones

Abstract

THE identification of either L-glutamate or L-aspartate as excitatory transmitters in the mammalian central nervous system would be facilitated by the discovery of specific antagonists of amino acid-induced and synaptic excitation. Hall et al. have suggested that D-α-aminoadipate may be an amino acid antagonist¹. They based their suggestion on the depressant effect of the DL form on spontaneous and amino acid-induced excitation of rat thalamic neurones, the L form being weakly excitatory. We have shown that related long-chain amino acids depress synaptic excitation of spinal neurones and exert a differential depressant action on chemically induced excitation of these cells². We therefore tested the actions of both D- and DL-α-aminoadipate on synaptically evoked excitation and on excitations induced by acetylcholine, L-glutamate, L-aspartate, kainate and N-methyl-D-asparate (NMDA) on spinal neurones. These latter two amino acids have been suggested to act on ‘glutamate-preferring’ and ‘aspartate-preferring’ receptors, respectively^3,4. The results presented here indicate that D-α-aminoadipate selectively antagonises NMDA- and L-aspartate-induced responses of dorsal horn interneurones and Renshaw cells and depresses non-cholinergic synaptic excitation of these cells evoked by dorsal root stimulation, whereas cholinergic excitation of Renshaw cells evoked by iontophoretic acetylcholine or ventral root stimulation is not depressed by this agent.