Amino acid transmitters Aspartate, GABA, Glutamate

To determine the contribution of the vesicular release pools to the K -induced increases in amino acid levels, Ca Mependency of the K -induced release was determined. About 50% of the K" -evoked release of both glutamate and GABA was Ca -dependent. In contrast, K -induced increases in the extracellular levels of the putative amino acid transmitters aspartate and taunne was completely Ca -independent (8). 

There are four amino acids (aspartate, GABA, glutamate, and glycine) that are strong transmitter candidates in brain. The difficulties in developing methods for studying their turnover are... 

There are more than 10 billion neurons that make up the human nervous system, and they interact with one another through neurotransmitters. Acetylcholine, a number of biogenic amines (norepinephrine, dopamine, serotonin, and in all likelihood, histamine and norepinephrine), certain amino acids and peptides, and adenosine are neurotransmitters in the central nervous system. Amino acid neurotransmitters are glutamic and aspartic acids that excite postsynaptic membrane receptors of several neurons as well as y-aminobutyric acid (GABA) and glycine, which are inhibitory neurotransmitters. Endorphins, enkephalins, and substance P are considered peptidergic transmitters. There are many compounds that imitate the action of these neurotransmitters. 

The dorsal horn of the spinal cord contains many transmitters and receptors. Some of these include peptides, eg. substance P, somatostatin and neuropeptide Y excitatory amino acids, e.g. glutamate and aspartate inhibitory amino acids, e.g. y-aminobutyric acid (GABA) nitric oxide endogenous opioids adenosine and the monoamines, e.g. serotonin and noradrenaline. There is, therefore, diverse therapeutic potential for... 

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... 

Evidence is lacking for the presence of the amino acids, y-aminobutyric acid (GABA), glutamic acid, aspartic acid and glycine, which are believed to play a role as transmitter substances in vertebrates and other invertebrates. 

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. 

As NJ eurotransmitters. Several amino acids serve as specialized neurotransmitters in both vertebrate and invertebrate nervous systems. These amino acids can be classified as inhibitory transmitters, such as y-aminobutyric acid [56-12-2] (GABA) and glycine, and excitatory amino acids, examples of which are L-glutamic acid and L-aspartic acid. A number of other amino acids and theic related substances occur in the brain and have some physiological activity. These include taurine [107-35-7], serine, profine, pipecofic acid [535-75-1], N-acetyl-aspartic acid [997-55-7], a- and p-alanines, and L-cysteine sulfinic acid [2381-08-0]. Eor more details about neurotransmitter amino acids, see reference 112. 

Several amino-acids are important neurotransmitters in the c.n.s. Glutamic and aspartic acids seem to be excitatory transmitters in the entire brain. y-Aminobutyric acid (GABA) and glycine are important inhibitory transmitters, the former in supraspinal interneurons and the latter at spinal interneurons (Curtis and Johnston, 1970). Of the polypeptide neurotransmitters, the most studied have been the endorphins and enkephalins (see Section 12.8), Substance P (an undecapeptide that helps transmit the sense of pain (von Euler and Pernow, 1977, somatostatin, and gastrin, and cholecystokinin whose action in the gut has been well researched. For more on GABA, see Section 12.7. 

The multiple pathways whereby the amino acid neuro-transmitters may be interconverted and the multiple compartments in which the amino acid neurotransmitters may be functional makes dynamic studies of glutamate, aspartate, and GABA a very difficult problem. So far, only GABA has been studied m detail. 

In order to characterize the transmitters in the optic nerve, we have monitored the release of amino acids from tissue slices of the supenor colliculus (SC). The levels of aspartate, glutamate, GABA, taurine, and p-alanine in the perfusate increased during depolarization with either 56 mM potassium (Fig 4) or veratri-dine. This increased release was Ca-dependent (Note not for taurine) and tetr odotoxin-sensitive (Sandberg and Jacobson, 1981). 

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