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Amino Acid Neurotransmitter Receptors

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  1. Introduction
  2. AMPA receptors
  3. Kainate receptors
  4. Metabotropic receptors
  5. Conclusion
  6. References

Glutamate Receptors Glutamate receptors are found throughout the brain and are expressed on both neurons and glia, although not all glutamate receptor subtypes are found on both cell types. Glutamate receptors, sometimes referred to as excitatory amino acid receptors, were initially classified into N-methyl-D-aspartate (NMDA), quisqualate, and kainate receptors on the basis of their preferential activation by these exogenous agonists. More recently, five categories of glutamate receptors (NMDA, kainate, a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid [AMPA], L-2-amino-4-phosphonobutyrate (L-AP4), and trans-1-aminocyclopentane-1,3-dicarboxylic acid [ACPD] receptors) have been established on the basis of pharmacological, electrophysiological, and molecular biological criteria. The L-AP4 receptor type is defined by its agonist and acts as an inhibitory autoreceptor, while the quisqualate receptors of the previous classification have been subdivided by means of more-specific agonists into AMPA and ACPD receptors. AMPA and Kainate receptors are sometimes collectively referred to as non-NMDA receptors. NMDA, kainate and AMPA receptors are ionotropic glutamate receptors; the L-AP4 and ACPD receptors are grouped as metabotropic receptors. Ionotropic receptors are ligand-gated cation-specific channels that are activated rapidly (milliseconds), whereas metabotropic receptors coupled to G proteins and second-messenger systems function more slowly on a scale of several hundred milliseconds to seconds.

[...] So far, the metabotropic receptor gene (mGluR) family has been shown to contain eight members, which are closely related in primary structure and can be divided into three groups on the basis of amino acid sequence homology, agonist sensitivity, and associated signal-transduction mechanisms. Group I receptors (mGlu1 and mGlu5) are coupled to the inositol triphosphate-Ca2+ cascade, while group II (mGlu2 and mGlu3) and group III (mGlu4 and mGlu6 through mGlu8) lead to the inhibition of adenylate cyclase. Some members of the mGluR families exist in alternatively spliced variants. [...]

[...] In addition to postsynaptic functions, kainate receptors act presynaptically on mossy fiber terminals within the hippocampus to generate epileptiform activity. NMDA Receptors NMDA receptors mediate excitatory neurotransmission in the CNS in different ways from AMPA and kainate receptors. They are characterized by voltage-dependent block by magnesium ions a high permeability to Ca2+, and slow gating kinetics. The NMDA receptor is a ligand-gated ion channel composed of two different subunits: NMDAR1 and NMDAR2. NMDAR1 can exist in seven splice variants, and there are four different genes encoding variants of NMDAR2 D). [...]

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