Amino acid transmitters in the mammalian central nervous system

120 D.R. CURTlS and G. A. R. JOHNSTON :
et al., 1971). Furthermore the natural occurrence of D-glutamate and D-aspartate in CNS tissue
has not been excluded (CORRIGAN, 1969).
L-Cysteate. The sulphonic acid analogue of L:aspartate is present in low concentration (approx.
0.1 /~mole/g) in extracts of rat brain (MussINI and MARCU¢¢k 1962; MANDEL and MARK, 1965).
This amino acid depolarizes feline spinal motoneurones and is comparable in potency to L-aspartate
(CURTIS et al., 1960). In general, L-cysteate may be metabolised by two pathways: decarboxylation
to taurine or transamination with a-oxo acids (GAITONDE, 1970). L-Cysteate is a strong competitive
inhibitor of the high affinity uptake of L-glutamate by rat brain slices and thus could be a substrate
for this transport system (BALCAR and JOHNSTON, 1972 b). L-Cysteate produces acute neuronal degeneration
in the hypothalamus of infant mice following subcutaneous administration (OLNEY et al.,
1971).
L-Cysteine Sulphinate. This acidic amino acid, which has been detected in rat brain (BERGERET
and CHAXAGNE, 1954)is a powerful excitant of spinal neurones (Cat: CURTIS and WATKINS, 1963)
and a powerful competitive inhibitor of the high affinity uptake of L-glutamate by rat brain slices
(BALeAR and JOHNSTON, 1972b). The enzyme L-cysteine sulphinate decarboxylase, which produces
hypotaurine from L-cysteine sulphinate, occurs in rat brain associated with synaptosomes (AGRAWAL
et al., 1971). The complex metabolic interrelations of L-cysteine sulphinate, L-cysteate, taurine and
hypotaurine are discussed by GAITONDE (1970). Subcutaneous administration of L-cysteine sulphinate
is followed by degeneration in the hypothalamus of infant mice (OLN~Y, HO and RHEE, 1971).
4. Anatomical Organization of Amino Acid Transmitters
4.1. Cerebral Cortex
4.1.1. Excitation
Although cortical glutamate levels (Table 2), are amongst the highest for mammalian
tissues, little evidence is currently available to associate regional differences
in the levels of either glutamate or aspartate with terminals of interneurones
or particular afferent fibres. Such arl association with fibres projecting to the
cortex is suggested bY the reduced levels of both amino acids (and GABA)
which follows undercutting of the suprasylvian gyrus in the cat (BERL and
MCMVRTRY, 1967), although the reduced glutamate levels of the motor cortex
of the cat as a result of tetanic stimulation of the thalamic ventrolateral nucleus
have been interpreted largely in terms of energy metabolism (CONSTANTINESCU,
FLOR~SCU, and HATEGANU, 1970). The moderate levels of glutamate in the corpus
callosum and the posterior portion of the internal capsule (Table 2), which exceed
those of the dorsal root, may indicate the presence of glutamate releasing fibres;
the low level in the peduncles suggest that the fibres of the pyramidal tract
may not be of this type.
Subcellular distribution studies have hitherto failed to demonstrate any selective
storage of either aspartate or glutamate within nerve endings (synaptosomes)
of the cerebral cortex (Rat: RYALL, 1964. Guinea pig: RYALL, 1964 ; MANGAN
and WHITTAKER, 1966; see also KRNJEVIC and WHITTAKER, 1965; WHITTAKER,
1968). Both amino acids, however, are accumulated from low extracellular concentrations
by a subcellular fraction of homogenates of this tissue which may
be largely synaptosomal in nature, and can be distinquished from fractions accumulating
other amino acids (Rat: WOFSEY et al., 1971). This "high affinity"