Amino acid transmitters in the mammalian central nervous system

164 D.R. CURTIS and G. A, R. JOHNSTON :
5.2. GABA
The most fully documented case for an amino acid transmitter, and indeed for
any central transmitter, is that for GABA, released at terminals of Purkinje
cell axons to inhibit Deiters' neurones. Somewhat less, though adequate, evidence
is available that GABA is an inhibitory transmitter in the cerebral, cerebellar
and hippocampal cortices released by basket type cells. In addition, GABA seems
likely to be an inhibitory transmitter in the substantia nigra (which contains
the highest levels of this amino acid in the brain), in the retina, olfactory bulb,
thalamic relay nuclei, dorsal column nuclei and the spinal cord. In the two
latter regions GABA is associated with prolonged inhibition, a process sensitive
to picrotoxinin and bicuculline, and which may be at least partially presynaptic
in nature.
5.3. Aspartate and Glutamate
Glutamate, the most abundant amino acid in the adult brain, and aspartate,
may be excitatory transmitters of the main afferent and efferent pathways within
the CNS. The evidence is far from convincing, the proposal being based largely
on negative evidence for the involvement of other substances, the distribution
of these amino acids in the brain and spinal cord, and the excitation by both
of neurones in all regions.
Neurochemical studies suggest that glutamate could be the excitatory transmitter
of spinal primary afferent fibres and aspartate a transmitter released by spinal
excitatory interneurones. Further investigations are required of the relative sensitivities
of central neurones to these excitants, a study confined so far to the thalamus
and spinal cord. Additionally there is a vital need for selective antagonists of
both the excitation by, and the uptake of, aspartate and glutamate in order
to establish the central pathways which operate by releasing these amino acids.
5.4. Other Amino Acids
It is possible that amino acids other than glycine, GABA, aspartate and glutamate
function as synaptic transmitters. These include ~- and fl-alanine, 7-aminobutyrylcholine,
cystathionine, cysteate, cysteine sulphinate, hypotaurine, taurine, imidazole-4-acetate
and serine. All influence the firing of neurones when administered
electrophoretically, and even the levels of those which occur in "trace" amounts,
in relation to GABA, are comparable with the amounts of acetylcholine, noradrenaline,
dopamine and 5-hydroxytryptamine in nervous tissue.
5.5. Concluding Remarks
This review has been concerned with the function of amino acids of relatively
simple chemical structure as excitatory and inhibitory transmitters regulating