Aspartate and glutamate
Aspartate and glutamate are the most abundant amino acids in the mammalian brain. While the precise role of aspartate in brain function is obscure, the importance of glutamate as an excitatory transmitter and as a precursor of GABA is well recognized. Despite the many roles which glutamate has been shown to play in intermediary metabolism and transmitter function, studies on the dentate gyrus of the hippocampal formation, where glutamate has been established as a transmitter, have shown that the synthesis of glutamate is regulated by feedback inhibition and by the concentration of its precursor glutamine. Thus the neuronal regulation of glutamate synthesis would appear to be similar to that of the ‘‘classical’’ transmitters. In the brain, there appears to be an inverse relationship between the concentration of glutamate and of GABA, apart from the context where both amino acids are present in low concentrations.
GABA
GABA is also present in very high concentrations in the mammalian brain, approximately 500mg/g wet weight of brain being recorded for some regions! Thus GABA is present in a concentration some 200–1000 times greater than neurotransmitters such as acetylcholine, noradrenaline and 5-HT. GABA is one of the most widely distributed transmitters in the brain and it has been calculated that it occurs in over 40% of all synapses. Nevertheless, its distribution is quite heterogeneous, with the highest concentrations being present in the basal ganglia, followed by the hypothalamus, the periaqueductal grey matter and the hippocampus; approximately equal concentrations are present in the cortex, amygdala andthalamus. GABA is present in storage vesicles in nerve terminals and also in the glia that are densely packed around nerve terminals, where they probably act as physical and metabolic ‘‘buffers’’ for the nerve terminals. Following its release from the nerve terminal, the action of GABA may therefore be terminated either by being transported back into the nerve terminal by an active transport system or by being transported into the glia. The rate of synthesis of this transmitter is determined by glutamate decarboxylase, which synthesizes it from glutamate. A feedback inhibitory mechanism also seems to operate whereby an excess of GABA in thesynaptic cleft triggers the GABA autoreceptor on the presynaptic terminal, leading to a reduction in transmitter release. Specific GABA-containing neurons have been identified as distinct pathways in the basal ganglia, namely in interneurons in the striatum, in the nigrostriatal pathway and in the pallidonigral pathway.
Aspartate and glutamate are the most abundant amino acids in the mammalian brain. While the precise role of aspartate in brain function is obscure, the importance of glutamate as an excitatory transmitter and as a precursor of GABA is well recognized. Despite the many roles which glutamate has been shown to play in intermediary metabolism and transmitter function, studies on the dentate gyrus of the hippocampal formation, where glutamate has been established as a transmitter, have shown that the synthesis of glutamate is regulated by feedback inhibition and by the concentration of its precursor glutamine. Thus the neuronal regulation of glutamate synthesis would appear to be similar to that of the ‘‘classical’’ transmitters. In the brain, there appears to be an inverse relationship between the concentration of glutamate and of GABA, apart from the context where both amino acids are present in low concentrations.
GABA
GABA is also present in very high concentrations in the mammalian brain, approximately 500mg/g wet weight of brain being recorded for some regions! Thus GABA is present in a concentration some 200–1000 times greater than neurotransmitters such as acetylcholine, noradrenaline and 5-HT. GABA is one of the most widely distributed transmitters in the brain and it has been calculated that it occurs in over 40% of all synapses. Nevertheless, its distribution is quite heterogeneous, with the highest concentrations being present in the basal ganglia, followed by the hypothalamus, the periaqueductal grey matter and the hippocampus; approximately equal concentrations are present in the cortex, amygdala andthalamus. GABA is present in storage vesicles in nerve terminals and also in the glia that are densely packed around nerve terminals, where they probably act as physical and metabolic ‘‘buffers’’ for the nerve terminals. Following its release from the nerve terminal, the action of GABA may therefore be terminated either by being transported back into the nerve terminal by an active transport system or by being transported into the glia. The rate of synthesis of this transmitter is determined by glutamate decarboxylase, which synthesizes it from glutamate. A feedback inhibitory mechanism also seems to operate whereby an excess of GABA in thesynaptic cleft triggers the GABA autoreceptor on the presynaptic terminal, leading to a reduction in transmitter release. Specific GABA-containing neurons have been identified as distinct pathways in the basal ganglia, namely in interneurons in the striatum, in the nigrostriatal pathway and in the pallidonigral pathway.
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