Inhibitory Amino Acid Neurotransmitters Glycine

In medicinal chemistry, the strychnine-insensitive receptor has received more attention. For example, the 5-nitro derivative of 6,7-dichloroquinoxalinedione has been identified as a highly potent antagonist of the glycine snbsite on the NMDA receptor. 

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A) Antagonism of the inhibitory amino acid neurotransmitter glycine... 

The amino acid neurotransmitters are subdivided into primarily excitatory (glutamate, aspartate) and inhibitory (y-aminobutyric acid, GABA, glycine) types. 

There is now evidence that the mammalian central nervous system contains several dozen neurotransmitters such as acetylcholine, noradrenaline, dopamine and 5-hydroxytryptamine (5-HT), together with many more co-transmitters, which are mainly small peptides such as met-enkephalin and neuromodulators such as the prostaglandins. It is well established that any one nerve cell may be influenced by more than one of these transmitters at any time. If, for example, the inhibitory amino acids (GABA or glycine) activate a cell membrane then the activity of the membrane will be depressed, whereas if the excitatory amino acid glutamate activates the nerve membrane, activity will be increased. The final response of the nerve cell that receives all this information will thus depend on the balance between the various stimuli that impinge upon it. 

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. 

Of the various amino acid neurotransmitters which have been implicated in epilepsy, the inhibitory transmitter glycine has been shown to be present in normal concentrations, or even slightly elevated, in the vicinity of the... 

Receptors for several neurotransmitters form ion-selective channels in the plasma membrane and diffuse their signals by altering the cell s membrane potential or the cytoplasmic ionic composition. This subfamily of receptors included the well-characterized nicotinic acetylcholine receptor from electric organ, muscle and brain, the receptors for the excitatory amino acids (aspartate and glutamate), the inhibitory amino acids (7-aminobutyrate (GABA), glycine). 

Picrotoxin has been instmmental in estabUshing an inhibitory neurotransmitter role for the amino acid, gamma-aminobutyric acid (GABA), quantitatively the most important inhibitory neurotransmitter in the mammalian CNS. Whereas glycine is predominately localized in the spinal cord, GABA... 

The amino acid glycine, a neurotransmitter at inhibitory synapses throughout the central nervous system (CNS),... 

Glycine is the simplest of all amino acids. It is involved in many metabolic pathways, is an essential component of proteins, and is found throughout the brain. A neurotransmitter role for glycine was first identified in the spinal cord, where it was found to be differentially distributed between dorsal and ventral regions and shown to cause hyperpolarisation of motoneurons (Werman et al. 1967). This inhibitory action of glycine is distinct from its... 

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). 

Glycine is in a class by itself. It is the only protein amino acid that is not chiral. It is neither hydrophilic nor hydrophobic. With the exception of proline, all other protein amino acids are derived from it by substituting various groups on the oi carbon atom. Glycine is an important inhibitory neurotransmitter in the central nervous system. 

In the human CNS, glutamate is the most important excitatory neurotransmitter. Glycine is a major inhibitory neurotransmitter in the human CNS. Thus, these two amino acids, basic constituents of proteins, also function in other very important ways in behavior, emotion, learning, memory, and sensory perception. Nature uses its molecular constructs for more than one purpose. Among other neurotransmitters, dopamine, epinephrine, norepinephrine, and serotonin are derivatives of protein amino acids and are synthesized from them. 

Glycine an amino acid commonly found in proteins and the most important inhibitory neurotransmitter in the human central nervous system. 

Several proteinogenic amino acids (see p. 60) have neurotransmitter effects. A particularly important one is glutamate, which acts as a stimulatory transmitter in the CNS. More than half of the synapses in the brain are glutaminergic. The metabolism of glutamate and that of the amine GABA synthesized from it (see below) are discussed in more detail on p.356. Glycine is an inhibitory neurotransmitter with effects in the spinal cord and in parts of the brain. 

Glycine A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH]... 

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... 

Tetanus is characterised by a prolonged contraction of skeletal muscle fibres the neurotoxin responsible is from Clostridium tetani. The toxin initially binds to peripheral nerve terminals and is then transported within the axon and across synaptic junctions until it reaches the central nervous system (CNS). Here it attaches to ganghosides at the presynaptic inhibitory motor nerve endings and is taken up into the axon by endocytosis. The effect of the toxin is to block the release of inhibitory neurotransmitters (glycine and gamma-amino butyric acid), which are required to check the nervous impulse, leading to the generalised muscular spasms characteristic of tetanus. 

Glycine, the smallest amino acid, is known to be an inhibitory neurotransmitter, but only a few studies investigated its role in pain modulation (Webb and Lynch,... 

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