Excitatory amino acid receptors in brain

Copani A., Canonico P L., Catania M. V., Aronica E., Bruno V., Ratti E., Van Amsterdam F. T. M., Gaviraghi G., andNicoletti F. (1991). Interaction between /3-N-methylamino-L-alanine and excitatory amino acid receptors in brain slices and neuronal cultures. Brain Res. 558 79-86. 

Gerber G, Cerne R, Randic M (1991) Participation of excitatory amino acid receptors in the slow excitatory synaptic transmission in rat spinal dorsal horn. Brain Res 567 236-251. 

Young, A.B. and Egg, G.E. (1991) Excitatory amino acid receptors in the brain membrane binding and receptor autoradiographic approaches. In D. Lodge and G.L. Collin-gridge (Eds.), Trends in Pharmacological Sciences. The Pharmacology of Excitatory Amino Acids, Special Report, Elsevier, Amsterdam, pp. 18-24. 

Antagonists of 2-amino-3-(3-hydroxy-5-methyl-4-isoxazoyl)proprionic acid (subset of excitatory amino acid receptors in the brain, of interest for treatment of neurodegenerative disease)... 

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... 

Excitatory transmitters such as glutamate utilize much of the energy demand of the brain and it is well established that excessive activation of central excitatory amino acid receptors may be neurotoxic even in the presence of normal glucose and oxygen. This type of neurotoxic damage is... 

Both phencyclidine and ketamine bind with high affinity to a number of receptors in the brain, but it is now accepted that the primary target is the sigma-PCP receptor site located in the ion channel of the NMDA excitatory amino acid receptor complex. The precise function of this receptor in the brain is still the subject of debate. It is now known that there are two distinct sigma receptor sites in the mammalian brain (ctj and a2) which are not associated with the NMDA receptor complex. Haloperidol and the atypical neuroleptic remoxipride bind with high affinity to such sites, and it has been postulated that some typical and atypical neuroleptics may owe some of their pharmacological effects to their action on such receptors. 

Herb, A., Burnashev, N., Werner, P., Sakmann, B., Wisden, W., and Seeburg, P. H. (1992). The KA-2 subunit of excitatory amino acid receptors shows widespread expression in brain and forms ion channels with distantly related subunits. Neuron 8, 775—785. 

Collins GG. 1982. Some effects of excitatory amino acid receptor antagonists on synaptic transmission in the rat olfactory cortex slice. Brain Res 244 311-318. 

This is the major fast-acting excitatory neurotransmitter with a wide distribution in the brain. There are four main types of excitatory amino acid receptors N-methyl D-aspartate (NMDA), amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), kainate (these all regulate cation channels) and metabotropic (G-protein coupled). There are many subtypes within these groups. 

Millan, M.H., Patel, S. and Meldrum, B.S. (1988) The involvement of excitatory amino acid receptors within the prepiriform cortex in pilocarpine-induced seizures in rats. Exp. Brain Res., 72, 517-522. 

The presence of o-serine in mammalian brain tissue was first reported in 1989 [33, 34]. It has recently been established that o-serine is employed in the mammalian forebrain as a co-agonist for the N-methyl-o-asparate (NMDA) excitatory amino acid receptor [35, 36]. A PLP-dependent serine racemase has been cloned and purified from mammalian brain, and found to be a homodimer, which has a number of nonessential cofactors that enhance its activity, including Ca +, Mg + and ATP [37-40]. The mouse brain enzyme has also been shown to catalyze elimination from L-serine, to form pyruvate, with an activity comparable to that for racemiza-tion [41]. Interestingly, the first instance of this class of racemase was discovered by Esaki and coworkers in the silkworm, Bombyx mori [42]. o-serine concentration in the blood of B. mori larvae is thought to play a role in metamorphosis. 

Earooqui AA, Horrocks LA (1991) Excitatory amino acid receptors, neural membrane phospholipid metabolism and neurological disorders. Brain Res Rev 16 171-191 Earooqui AA, Horrocks LA (1994) Excitotoxicity and neurological disorders involvement of membrane phospholipids. Int Rev Neurobiol 36 267-323 Earooqui AA, Ong WY, Horrocks LA (2004) Biochemical aspects of neurodegeneration in human brain involvement of neural membrane phospholipids and phospholipases A2. Neurochem Res 29 1961-1977... 

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