Amino acid transmitters in the mammalian central nervous system

162 D.R. CURTIS and G. A. R. JOHNSTON :
SCHON, 1973 b). When incubated with labelled amino acids cat and rat ganglia
accumulate GABA by a high affinity system (Kmapprox. 2.5 x 10-5M) which
is facilitated by amino-oxyacetic acid and occurs predominantly into satellite
glial cells (GOTTESFELD et al., 1973 b). In contrast, e-alanine and glycine transport
is less rapid and occurs into both glial cells and neurones.
When administered by close intra-arterial injection, GABA depolarizes the
nodose ganglion of the cat, the threshold dose being 0.05-2 gg (DE GROAT, 1972).
No action could be demonstrated for higher doses of glycine, L-glutamate, L-
aspartate or DL-homocysteate, and the depolarizing action of GABA was abolished
by picrotoxin (100 300 lag) or bicuculline (100-300 lag) but was unaffected
by strychnine (200-400 lag). Essentially similar results were obtained using lumbar
dorsal root ganglia when GABA was administered intra-arterially or intravenously
(Cat: DE GROAT, LALLEY, and SAUM, 1972), threshold concentrations
of GABA after intravenous administration being of the order of 10-7-10-6 M.
Depolarization by 3-aminopropane sulphonic acid, fl-alanine and &aminovaleric
acid were also demonstrated (DE GROAT et al., 1972). Furthermore electrophoretic
GABA depolarizes cultured dorsal root ganglion cells, an effect also blocked
by picrotoxin (O~ATA, 1972 a).
This depolarizing action of GABA, which appears not to modify impulse
transmission through sensory ganglia (DE GROAT et al., 1972), has been interpreted
in terms of enhanced chloride permeability (DE GROAT, 1972), and the relevance
of this apparently non-synaptic change in membrane potential to the depolarization
of central terminals of afferent fibres during "presynaptic" inhibition (see
Section 4.12.3.2) remains to be determined. Neuronal or glial uptake with a
subsequent elevation of extracellular potassium levels seems unlikely since neither
picrotoxin nor bicuculline interfere with GABA uptake elsewhere in the nervous
system.
4.13.2. Autonomic Ganglia
Earlier evidence of the effects of amino acids upon autonomic ganglia has been
discussed previously (CURTIS and WATKINS, 1965).
The very low concentrations ofGABA ( < 0.1 lamole/g, Rat: NAGATA, YOKOI,
and TSUKADA, 1966; MASI, PAGGI, POCCHIAR, and ToscHL 1969; MCBRIDE and
KL~NGNAN, 1972) and GAD (NAGATA et al., 1966) within the superior cervical
ganglion could be considered to exclude a functional role of this amino acid
in such ganglia. Nevertheless, isolated ganglia accumulate GABA by a relatively
high affinity sodium dependent system which however differs in substrate specificity
from that of brain tissue (Rat: superior cervical ganglion, BOWERY and
BROWN, 1972 b). The uptake is not modified by preganglionic denervation (Bow-
ERY and BROWN, 1972b) and uptake into nerve terminals also seems excluded
in radio-autographic studies, the amino acid being located in neurones and capsular
cells (BowERY and BROWN, 1971). An equivalent or greater accumulation
of GABA was demonstrated for the preganglionic cervical sympathetic trunk
and the vagus nerve (BOWERY and BROWN, 1972 b). Although electrical stimulation
of pre- or postganglionic trunks, or treatment with carbamylcholine, did not