Excitatory amino acids neurophysiology

The red alga Digenea simplex has been used for the treatment of roundworm disease for centuries. Its active principle is kainic acid. The related domoic acid is a constituent of another red alga, Chondria armata, used for the same purpose. These compounds, known as kainoids, are potent neurotoxins and excitatory amino acids. Kainoids are important tools in neurophysiological research. Domoic acids are also produced by diatoms and were responsible for the shellfish poisonings known as amnesic shellfish poisonings that occurred in Canada in 1987. 

Before discussing the excitotoxins, the neurophysiologic effects of excitatory amino acids will be reviewed since this provides a conceptual background for understanding the mechanism of action of these compounds. More than 70 a-amino acids have been shown to have excitatory effects in the vertebrate central nervous system (Table 1) with the recent... 

From the neurophysiologic and ligand-binding studies, it is apparent that there are a number of receptors that mediate the excitatory effects of acidic amino acids and their conformationally restricted or synthetic analogs. As noted by Watkins (1978), the flexibility of the linear acidic amino acids such as glutamic acid may allow them to assume a variety of conformations capable of binding to subpopulations of these receptors, some of which are selectively activated by the conformationally restricted analogs. While neuronal excitation appears to be a property common to all the acidic amino acids, specific receptors could also activate distinct sets... 

Neurophysiologic and neuropharmacologic studies indicate that N-methy 1-Dr aspartic acid (NMD A) activates a distinct set of excitatory receptors that differ from those sensitive to either quisqualic acid or kainic acid. The excitatory effects of NMDA are selectively antagonized by the divalent cation Mg as well as by D-a-amino adipate and the more potent 2-amino-4-phosphonovaleric acid (Davies et al., 1979). Olney and co-workers (1971)... 

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