Glutamate, as neurotransmitter

Ericson AC, Blomqvist A, Craig AD, Ottersen OP, Broman J (1995) Evidence for glutamate as neurotransmitter in trigemino- and spinothalamic tract terminals in the nucleus submedius of cats. Eur J Neurosci 7 305-317. 

Fonnum F, Storm-Mathisen J, Divac I (1981) Biochemical evidence for glutamate as neurotransmitter in corticostriatal and corticothalamic fibres in rat brain. Neuroscience 6 863-873. 

Aspartate is closely related metabolically and chemically to glutamate. In many respects it is difficult to differentiate between aspartate and glutamate as neurotransmitter candidates (Fonnum, 1984). There are, however, some fibers and terminals in which aspartate is regarded as a stronger transmitter candidate than glutamate. These include the cerebellar climbing fibers (Wiklund et al., 1982), hippocampal commissural fibers (Nadler et al., 1978), olfactory tract (Collins and Probett, 1981), cochlear nucleus afferents (Wenthold, 1979), and spinal cord intemeurons (Davidoff et al., 1967)... 

Nobody can ever say that. It is known that the human body uses glutamates as neurotransmitters in the brain (see pl69 and p451), and they are believed to be linked to memory retrieval. In fact, every m or organ in the body contains glutamate receptors. 

Certain amino acids and their derivatives, although not found in proteins, nonetheless are biochemically important. A few of the more notable examples are shown in Figure 4.5. y-Aminobutyric acid, or GABA, is produced by the decarboxylation of glutamic acid and is a potent neurotransmitter. Histamine, which is synthesized by decarboxylation of histidine, and serotonin, which is derived from tryptophan, similarly function as neurotransmitters and regulators. /3-Alanine is found in nature in the peptides carnosine and anserine and is a component of pantothenic acid (a vitamin), which is a part of coenzyme A. Epinephrine (also known as adrenaline), derived from tyrosine, is an important hormone. Penicillamine is a constituent of the penicillin antibiotics. Ornithine, betaine, homocysteine, and homoserine are important metabolic intermediates. Citrulline is the immediate precursor of arginine. 

After an overview of neurotransmitter systems and function and a consideration of which substances can be classified as neurotransmitters, section A deals with their release, effects on neuronal excitability and receptor interaction. The synaptic physiology and pharmacology and possible brain function of each neurotransmitter is then covered in some detail (section B). Special attention is given to acetylcholine, glutamate, GABA, noradrenaline, dopamine, 5-hydroxytryptamine and the peptides but the purines, histamine, steroids and nitric oxide are not forgotten and there is a brief overview of appropriate basic pharmacology. 

The following substances, listed alphabetically, have been widely implicated and generally accepted as neurotransmitters in the central nervous system (CNS), although some, such as glutamate, are much more important than others, e.g. adrenaline. Some... 

Amino acid There are 20 different amino acids that provide the building blocks of proteins. Three of them - aspartate, glutamate and glycine (together with GABA, or y-aminobutyric acid) also function as neurotransmitters. 

An overview of some of the processes involved in synaptic transmission is shown in Figure 10-1. Many of the processes are discussed below or in other chapters of this book. Many different types of substance are neurotransmitters. Classical neurotransmitters, such as ACh (see Ch. 11) and norepinephrine (NE see Ch. 12), are low-molecular-weight substances that have no other function but to serve as neurotransmitters. The predominant excitatory neurotransmitter in the brain, glutamate, and the inhibitory neurotransmitter in the spinal cord, glycine, are common and essential amino acids (see Chs 15 and 16). 

Glutamate. Inputs to the basal ganglia, from the cortex, PPN and CM/Pf, as well as intrinsic projections from the STN, utilize glutamate as a neurotransmitter (Fig. 46-1). 

Nedergaard M, Takano T, Hansen AJ (2002) Beyond the role of glutamate as a neurotransmitter. Nat Rev Neurosci 3 748-755... 

A marked and initial loss of long pyramidal neurons in layer II has been observed in the brain cortex. These neurons are predominantly involved in the corticocortical connections and probably use aspartic and glutamic acid as neurotransmitters (Maragos et al. 1987). 

Phosphonates have been widely used as analogues of carboxylic acids. They have been particularly effective as analogues of tetrahedral transition states that occur in the course of enzyme-catalyzed reactions such as hydrolysis of the amide (peptide) bond. As such, they may be used as inhibitors of enzymes (e.g., 82, 83) or as haptens for producing antibodies that are catalytic (e.g., 84). A notable example is H203P— CH2—CH2—CH(—NH2)—COOH, which has effects that are likely to be due to its interference with glutamate as a neurotransmitter (85). 

Amino acids as neurotransmitters. The concentrations of glutamate and of its decarboxylation product y-aminobutyrate (GABA) are high in all regions... 

In brain tissue, low concentrations of glutamate and aspartate perform as neurotransmitters, but at high concentration these amino acids act as neurotoxins. Major advances in the excitatory amino acid receptor field have come from the identification, characterization, and cloning of different families of receptors and transporters (Dingledine and McBain, 1999). These receptors and transporters are specialized... 

---