Glutamate/glutamic acid transmitter function

Other neurotransmitters. The abundant glutamate, GABA, and glycine are major neurotransmitters. Do other amino acids also function in the brain Roles for L-aspartate and D-serine (p. 1785) have been identified, but it is very difficult either to discover or to disprove a neurotransmitter function for other amino acids. It is even more difficult for small amounts of various amines and small peptides that are present in the brain. Taurine (Fig. 24-25) is one of the most abundant free amino acids in animals and meets several criteria for consideration as both an inhibitory and an excitatory transmitter.797 798 However, its function is still uncertain (see Chapter 24). Homocysteic acid, formed by oxidation of homocysteine, is a powerful neuroexcitatory substance, but its concentration in the brain is very low.149 d-Aspartate is also present... 

So far attention has concentrated on the effects of lithium on excitatory transmitters. There is evidence that the drug can also facilitate inhibitory transmission, an effect that has been attributed to a desensitization of the pres)maptic gamma-aminobutyric acid (GABA) receptors, which results in an increase in the release of this inhibitory transmitter. The increased conversion of glutamate to GABA may also contribute to this process. Thus it would appear that lithium has a varied and complex action on central neurotransmission, the net result being a diminution in the activity of excitatory transmitters and an increase in GABAergic function. 

Several amino acids are broken down by de-carbo qflation. This reaction gives rise to what are known as biogenic amines, which have various functions. Some of them are components of biomolecules, such as ethanolamine in phospholipids (see p. 50). Cysteamine and T-alanine are components of coenzyme A (see p.l2) and of pantetheine (see pp. 108, 168). Other amines function as signaling substances. An important neurotransmitter derived from glutamate is y-aminobutyrate (GABA, see p.356). The transmitter dopamine is also a precursor for the catecholamines epinephrine and norepinephrine (see p.352). The biogenic amine serotonin, a substance that has many effects, is synthesized from tryptophan via the intermediate 5-hydroxytryptophan. 

FIGURE 7-41 Structures of several small molecules that function as neurotransmitters. Except for acetylcholine, all these are amino acids (glycine and glutamate) or derived from the indicated amino acids. The three transmitters synthesized from tyrosine, which contain the catechol moiety (blue highlight), are referred to as catecholamines. 

In addition to the monoamines NE, DA, 5HT, and possibly histamine that function as neurotransmitters in the CNS, a number of amino acids (and peptides) with likely neurotransmitter credentials exist. GABA among these is the best documented. Others may be considered as putative or even simply as transmitter candidates at this point. Amino acids such as glycine (gly), serine (ser), glutamate (glu), aspartate (asp), taurine, substance P (SP), and others may be included here. 

For a growing number of neurotransmitters, direct neurotrophic actions have been reported (for a review see Schwartz, 1992 Schwartz and Tani-waki, 1994). These transmitters are serotonin, acetylcholine, norepinephrine, glutamate and endogenous opioid peptides. Some of these neurotrophic transmitters may also be produced by astrocytes. The family of neurotransmitters synthesized by astrocytes comprises y-aminobutyric acid, glutamate, proenkephalin, neuropeptide Y, somatostatin and others. Martin (1992) has coined the term gliotransmitter for such substances. The role of gliotransmission in development and function of the mature nervous system has not been firmly established yet. It can be anticipated, however, that neurotrophic activity of astroglia-derived transmit-... 

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