An evaluation of selected brain constituents as putative excitatory neurotransmitters

Searching for the endogenous ligands of the 4 classes of excitatory amino acid receptors detected in the mammalian CNS, we have measured, using a ²²Na⁺ efflux receptor assay, the excitatory activty of 42 brain constituents or analogs and established the receptor specificity of those substances which possess excitatory properties. Among the substances tested were methyltetrahydrofolate and N-acetylaspartylglutamate, two putative ligands of the kainate and glutamate receptors. These compounds were found to have very little or no excitatory activity, respectively. The 8 brain constituents possessing excitatory properties displayed a receptor specificity similar to either that of N-methyl-d-aspartate (e.g.quinolinate) or glutamate (e.g. cysteine sulfinate)_but not of kainate or quisqualate. These results are discussed in relation with the problem of the identification of brain excitatory neurotransmitters.