Amino acid transmitters in the mammalian central nervous system

Amino Acid Transmitters in the Mammalian Central Nervous System 115
(Rat: SHAW and HEINE, 1965; SHANK and APRISON, 1970). L-Serine is also concerned with the
metabolism of L-cystathionine (GAITONDE, 1970). Intraperitoneally administered glycine (13 pmole/g)
raises the central levels of serine (Rat: RICHTER and WAINER, 1971).The rate of entry of serine
from the blood into the brain of immature rats is 40-120 times that of mature rats (BA~oS et
al., 1971). When administered electrophoretically L-serine is a weak strychnine-sensitive depressant
of the firing of feline spinal neurones (CURTIS et al., 1968a). L-Serine does not influence the high
affinity uptake of glycine by slices of cat and rat spinal cord (JOHNSTON and IVERSEN, 1971 ; BALCAR
and JOHNSTON, 1973), and is itself taken up by a "low affinity" system (Km approx. 6 × 10-4M)
into slices and homogenates of rat cord (JOHNSTON and IVERSEN, 1971 ; LOGAN and SNVDER, 1972).
L-Cystathionine. The levels of L-cystathionine in the CNS vary over a wide range, with high
levels in the cerebellum (Rat: SHAW and HEINE, 1965; KANDERA, LEVI, and LAJTHA, 1968) and
the bovine pineal body (LABELLA, VIVIAN, and QUEEN, 1968). Spinal levels in cats (WERMAN, DAVIDOFF,
and APRISON, 1966) were overestimated by a factor of ten (WERMAN, 1972). L-Cystathionine has
a relatively weak, strychnine-sensitive, depressant action on the firing of feline spinal neurones (WER-
MAN, DAVIDOFF, and APRISON, 1966; CURTIS et al., 1968a). When intravenously administered, it
is not transported into the brain but metabolic degradation products are incorporated into brain
protein (Rat: BROWN and GORDON, 1971).
Hypotaurine. This sulphinic acid, a metabolic precursor of taurine, has been detected in extracts
of rat brain (BERGERET and CHATAGNE, 1954). Hypotaurine depresses the firing of feline spinal
neurones (CURTIS and WATKINS, 1965), and inhibits the uptake of taurine by rat brain slices (KACZ-
MAREK and DAVISON, 1972).
fl-Alanine. Very low levels of this amino acid occur in the CNS (TALLAN, 1962; Human: PERRY
et al., 1971 a. Cat: PERRY et al., 1972. Rat: SCHENCK, 1943; YOSHINO, DEFEUDIS, and ELLIOTT, 1970).
The hyperpolarization by fl-alanine of feline spinal motoneurones is similar to that of glycine (CURTIS
et al., 1968b). In the feline spinal cord and lateral vestibular nucleus the depressant action of
fl-alanine is antagonised by strychnine and unaffected by bicuculline, but in the thalamus and in
the cerebral, cerebellar and hippocampal cortices, this action is antagonised by both alkaloids (CURTIS
et al., 197l a, b).
7-Aminobutyrylchotine. This GABA derivative, present in the brain, has little or no depressant action
in the cat on the firing of spinal interneurones or neurones of the cerebral cortex, but does influence
the firing of Renshaw ceils in the spinal cord. These and other observations suggest that the pharmacological
actions of this compound in the CNS may be related to cholinergic systems rather than
to those involving GABA (JOHNSTON and CURTIS, 1972).
7-Amino-fl-hydroxybutyric Acid. While the betaine carnitine undoubtedly occurs in the brain,
controversy still surrounds the role (HAYASHI, 1966), and even the presence (BAXTER, 1970; Mouse,
ox: SELLER and WIECHMANN, 1969. Rat: YOSHINO, DEFEUDIS, and ELLIOTT, 1970) of y-amino-flhydroxybutyric
acid in nervous tissue. It is not a substrate for GABA-T (Rat: SYTINSKY and VASILHEV,
1970; BEART and JOHNSTON, 1973a) and can be only a relatively weak substrate for the GABA
uptake system in rat brain slices (IVERSE~ and JOHNSTON, 1971). The amino acid is a weaker depressant
of the firing of central neurones than is GABA, and this action is antagonised by bicuculline but
not by strychnine (Cat: CURTIS et al., 1971 a, b).
lmidazole-4-acetic Acid. This histamine metabolite (KAHLSON and ROSENGREN, 1971) structurally
resembles both GABA and fl-alanine. Following parental administration, imidazole-4-acetic acid
has mixed excitant and depressant effects (Mice, rats: TUNNICLIFF, WEIN, and ROBERTS, 1972),
although, on electrophoretic administration the firing of neurones in the feline spinal cord, cerebral
cortex and medulla is depressed, an effect comparable in potency to GABA and suppressed by
bicuculline (PHILLIS, TEBECIS, and YORK, 1968; CURTIS et al., 1971a, b; HAAS, ANDERSON, and
H6SLI, 1972). Imidazole-4-acetic acid is a weak inhibitor of GABA uptake into slices of spinal
cord (Cat: BALCAR and JOHNSTON, 1973), and of rat brain GAD I (SMALL, HOLTON, and ANCILL,
1970).
2,4-Diaminobutyric acid. This amino acid has been detected in brain (Ox : NAKAJIMA, WOLFGRAM
and CLARK, 1967), is a weak depressant of spinal interneurones (Cat: CURTIS and WATKINS, 1960)
and a comparatively strong non-competitive inhibitor of the uptake of GABA by rat brain slices
(IVERSEN and JOHNSTON, 1971).