Amino acid transmitters

Noradrenaline transporters (NAT) are localized in the presynaptic plasma membrane of adrenergic nerve terminals. They belong to a family of proteins with 12 putative transmembrane proteins which are responsible for recycling of released neurotransmitters (noradrena-line/adrenaline, dopamine, serotonin, amino acid transmitters) back into the presynaptic nerve ending. Noradrenaline transporters can be blocked by a number of different antidepressant drags, including tricyclic antidepressants (e.g. desipramine) and selective noradrenaline reuptake inhibitors (e.g. reboxetine). 

Phyllis, JW, Smith-Barbour, M and O Regan, MH (1996) Changes in extracellular amino acid transmitters and purines during and following ischemias of different durations in the rat cerebral cortex. Neurochem. Int. 29 115-120. 

In other experiments, we found that PCP also inhibited ACh release induced by the amino acid transmitter candidates, L-glutamate and L-aspartate. Release of ACh by these amino acids had a similar Mg++sensitivity to that induced by NMDA, suggesting an action of these amino acids on the N-type receptor. No inhibition of release by PCP could be seen in the presence of Mg++. 

Kombian SB, Warenycia MW, Mele FG, et al. 1988. Effects of acute intoxication with hydrogen sulfide on central amino acid transmitter systems. Neurotoxicology 9 587-595. 

Watkins, J. C. and Evans, R. H. (1981) Excitatory amino acid transmitters. Anna. Rev. Pharmacol. Toxicol. 21,165-204. 

Knowledge of the mechanisms whereby the amino acid transmitters produce their effects has been valuable in the development of psychotropic drugs that may improve memory, reduce anxiety, or even counteract the effects of post-stroke hypoxia on brain cell survival. Some of these aspects are considered later. 

The principal amino acid transmitters and their metabolic inter-relationships are shown in Figure 2.20. 

These amino acid transmitters are predominant, accounting for most of the fast synaptic transmission in the brain. Together they occur in 70-80% of cerebral neurons. The concentration of GABA is for example up to 1000 times greater than that of other transmitters like acetylcholine or dopamine. 

Thus there is evidence, albeit circumstantial, of a disturbance of glutamate systems in the disease. In addition there is evidence of GABAergic deficits. Adding to the relevance of these hypotheses of amino acid transmitter dysfunction is the opportunity to relate neurochemical changes directly to a neuronal pathology and, with some further extrapolation, to the aetiology of schizophrenia. 

Other CNS transmitter systems, particularly some of the amino acid transmitters, in some of the above-mentioned ways to produce their effects. 

B) The predominance of glycine as an inhibitory amino acid transmitter in the spinal cord... 

C. Glycine is the major inhibitory amino acid transmitter in the spinal cord, and strychnine is a relatively selective antagonist of glycine. Strychnine has very little if any action at the GABA receptor-chloride channel complex. 

N. A. Sharif (1985). Multiple synaptic receptors for neuroactive amino acid transmitters—new... 

Alger, B.E, and Harms Mohler Pharmacology of Inhibmry Amino Acid Transmitters, Springer- Verlag Inc., New York, NY, 2000. 

The properties of classical neuro transmitters, as described for ACh and NE, can be applied with some variations to numerous other substances which have subsequently been determined to act as neurotransmitters. For example, in the case of amino acid transmitters such as GABA or glutamate, we would note that much of the released neuro transmitter is cleared from synapses by high affinity uptake into glial cells (astrocytes), in addition to nerve terminals. Peptide neurotransmitters, such as one of the endor-... 

Assay of ATP-dependent uptake of catecholamines or amino acid transmitters... 

GABA Gamma-amino-butyric acid, an inhibitory amino acid transmitter associated with synaptic depression... 

Glutamate Primary excitatory amino acid transmitter in the CNS associated with synaptic development, fast synaptic transmission, memory, and excitotoxicity when present in excessive amounts. 

The present communication is intended as a brief overview of the literature pertaining to amino acid transmitter candidates. Interested readers are urged to consult any of a number of excellent reviews. 

Krnjevic K (1986) Amino acid transmitters 30 years progress in research. In Iversen LL, Goodman E (Eds), Fast and Slow Signalling in the Nervous System. Oxford Oxford University Press, pp 3-15. 

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