Amino acid transmitters in the mammalian central nervous system

150 D.R. CURTIS and G. A. R. JOHNSTON:
4.12.1.1. Aspartate
Within the cord ventral grey levels are higher than dorsal grey. An association
with small neurones, presumably interneurones, has been suggested by the significant
reduction in aspartate produced by temporary aortic occlusion, the reduced
levels of this amino acid in dorsal and ventral grey matter correlating with the
reduced count of small neurones in the central grey region (DAvIDOFF et al.,
1967).
As shown in Table 9 the activity of aspartate aminotransferase does not
seem to correspond closely with that of the amino acid (Table 8).
4.12.1.2. Glutamate
L-Glutamate is the only putative amino acid transmitter for which dorsal root
levels exceed those of the ventral root (Table 8), as might be expected of a
transmitter released by primary afferent fibres. Similar differences occur in the
dog and rat (DUGGAN and JOHNSTON, 1970b). The high level of the amino acid
in dorsal root ganglia, and the gradient along the root (Cat': ganglion 4.5 #mole/g,
dorsal root distal to cord 4.5, proximal to cord 3.4, DUGGAN and JOHNSTON,
1970a), which contrasts to the approximately equal levels of other amino acids
in peripheral nerves and dorsal roots (Table 8), suggests that glutamate synthesised
in ganglion cells is transported towards central terminals. No such dorsal root
gradient was present in thedog (DuGGAN and JOHNSTON, 1970b). Further investigation
is warranted of the relationship to the possible transmitter function of glutamate
of the influx into, and particularly the efflux from, stimulated peripheral
nerves (WHEELER, BOYARSKY, and BROOKS, 1966; DEFEUDIS, 1971 ; WHEELER and
BOYARSKY, 1971).
After aortic occlusion, and loss of spinal interneurones, glutamate levels fall
significantly in all segments of the cord, especially in the dorsal grey, but no
correlation could be established between neurone loss and change in amino acid
concentration (DAvIDOFF et al., 1967). Furthermore spinal glutamine levels were
not modified (Table 8). The pattern of activity of glutamine synthetase and glutaminase
(Table 9), enzymes associated with glutamate-glutamine interconversion,
and of glutamate dehydrogenase, correspond with the distribution of glutamine,
but not with that of glutamate (Table 8).
Both high and low affinity uptake mechanisms are present in spinal tissue
for acidic amino acids, the same high affinity process transporting L-glutamate
and L-aspartate (Rat: LOGAN and SNYDER, 1972. Cat: BALCAR and JOHNSTON,
1973). Osmotically sensitive particles of density similar to that of nerve endings
are in part responsible for this uptake, which in the cat is less sensitive to
inhibition by p-chloromercuriphenylsulphonate than the high affinity uptake
of either glycine or GABA. In the rat the particles accumulating aspartate and
glutamate are denser than those accumulating glycine (ARREGUI et al., 1972).
4.12.1.3. Glycine
In contrast to relatively low levels in dorsal and ventral roots, higher levels
of glycine are found in the spinal grey matter, particularly ventrally (Table 8).