Neurophysiology, amino acids

The recently identified brain-specific isoform of metallothionein, MT-III (neuronal growth inhibitory factor, GIF), has been linked with its potential role in neurophysiological and neuromodulatory functions (484). The human form of MT-III contains 68 amino acids with a 70% sequence (Fig. 23) similarity to other mammalian MTs and a... 

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. 

Cone snails, Conus spp., have been investigated because of their production of conotoxin peptides. From an evolutionary standpoint, the production of conotoxins is quite interesting due to their wide range of neurophysiological activities. The conotoxins are small peptides, 10-30 amino acids, with conformations constrained by multiple disulfide bonds that target a number of receptors in vertebrate and invertebrate nervous systems. Cone snails use these toxins to immobilize prey, which allows the relatively slow-moving cone snails to feed on fish and worms. The wide variety of conotoxins isolated and the hypervariability within peptide sequences has led some to hypothesize a combinatorial biosynthetic approach for the production of conotoxins.116117... 

Higuchi, K., Shimizu, Y., Nambu, S., Miyabayashi, C., Takahara, T., Saito, S., Hioki, O., Kuwabara, Y., Watanabe, A. Effects of an infusion of branched-chain amino acids on neurophysiological and psychometric testings in cirrhotic patients with mild hepatic encephalopathy. 

The zebrafish, Danio rerio, was chosen as model of a simple vertebrate olfactory system. Zebrafish use their sense of smell in feeding, predator detection and reproduction (van den Hurk et al. 1987), and many naturally relevant odorants are known, such as amino acids, bile acids, nucleotides and pheromones (Carr 1988). We have used a combination of neuroanatomical, molecular biological and neurophysiological techniques to characterize spatial patterns in the olfactory epithelium and the olfactory bulb of zebrafish. 

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... 

If we now return to the question initially posed in this chapter is taurine a neurotransmitter , it emerges clearly that much more work is necessary before an adequate answer could be given. However, if we compare taurine responses with those of amino acids for which a role as neurotransmitter seems well established, like GABA or glycine, it seems that if taurine is actually acting as a synaptic transmitter, the extent of its involvement in such a role is rather restricted. Its neurophysiological action is weak, its release upon depolarization is controversial and probably calcium-independent and, most importantly, taurine postsynaptic receptors appear to be very scarce. Therefore, it may be considered that the main role of taurine in the CNS is not that of a neurotransmitter, althou such an action in restricted areas cannot be ruled out. 

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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