Excitatory amino acid receptor metabotropic

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Laudrup P, Kiitgaard H. (1993). Metabotropic and ionotropic excitatory amino acid receptor agonists induce different behaviorai effects in mice. EurJ Pharmacol. 250(1) 15-22. 

Zheng, F., Gallagher, J.P., Connor, J.A. Activation of a metabotropic excitatory amino acid receptor potentiates spike-driven calcium increases in neurons of the dorsolateral septum, J. Neurosci. 1996, 16, 6079-6088. 

Schoepp D., Bockaert J., and Sladeczek F. (1990). Pharmacological and functional characteristics of metabotropic excitatory amino acid receptors. Trends Pharmacol. Sci. 11 508-515. 

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. 

Brauner-Osborne, H., Nielsen, B., Stensbol, T.B., Johansen, T.N., Skjaer-baek, N., Krogsgaard-Larsen, P., 1997. Molecular pharmacology of 4-substituted glutamic acid analogues at ionotropic and metabotropic excitatory amino acid receptors. Eur. J. Pharmacol. 335. R1-R3. 

Expression of the human excitatory amino acid transporter 2 and metabotropic glutamate receptors 3 and 5 in the prefrontal cortex from normal individuals and patients with schizophrenia. Brain Res Mol Brain Res 56 207-217. 

Ohnuma T, Kato H, Arai H, Faull RL, McKenna PJ, et al. 2000a. Gene expression of PSD95 in prefrontal cortex and hippocampus in schizophrenia. Neuroreport 11 3133-3137. Ohnuma T, Tessler S, Arai H, Faull RL, McKenna PJ, et al. 2000b. Gene expression of metabotropic glutamate receptor 5 and excitatory amino acid transporter 2 in the schizophrenic hippocampus. Brain Res Mol Brain Res 85 24-31. 

The excitatoiy amino acids (EAA), glutamate and aspartate, are the principal excitatory neurotransmitters in the brain. They are released by neurons in several distinct anatomical pathways, such as corticofugal projections, but their distribution is practically ubiquitous in the central nervous system. There are both metabotropic and ionotropic EAA receptors. The metabotropic receptors bind glutamate and are labeled mGluRl to mGluRB. They are coupled via G-proteins to phosphoinositide hydrolysis, phospholipase D, and cAMP production. Ionotropic EAA receptors have been divided into three subtypes /V-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazole-proprionic acid (AMPA), and kainate receptors (Nakanishi 1992). 

The amino acid L-glutamate is the main excitatory neurotransmitter of the central nervous system (Fonnum, 1984). Glutamate exerts its excitatory effects either by activation of several G-protein-coupled metabotropic glutamate receptors or by induction of ion fluxes by different classes of ionotropic receptors. The NMDA receptor is one of those glutamate-gated ion channels which got its name from its selective artificial agonist NMDA (N-methyl-D-aspartate) and which controls slow but persistent ion fluxes of Na+, K+, and Ca2+ across the cell membrane. 

Metabotropic glutamate receptors act via G proteins and a variety of different types have been resolved. Class I (subtypes 1 and 5), Class II (subtypes 2 and 3), Class III (subtypes 4, 6, 7 and 8) and phospholipase D (PLD)-coupled mGlu-Rs couple through G proteins to increase PLC via Gao/Gaq (Class I), decrease adenylyl cyclase via Gai (Classes II and III) and to increase PLD-coupled mGlu-R. The glutamate receptors are excitatory and agonists can be neurotoxic. such as Amanita-derived ibotenic acid and the Guam cycad amino acid BMAA ((3-jV-methylamino-i-alanine), which causes a type of dementia (Table 5.5). 

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