Glutamate Receptors

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All about glutamate receptors

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PRESENTATION ON GLUTAMATE RECEPTORS PRESENTED TO PRESENTED BY TALAH JAWAID SIR CHETAN RASTOGI

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Glutamate These are Excitatory Amino Acid. Principal excitatory neurotransmitter in CNS, stored in neuronal cell membrane. Glutamate comes into the CNS mainly by glial cells and by Kreb’s cycle. Responsible for neural communication, memory formation, learning, and regulation

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GLUTAMATE SYNTHESIS Glutamine comes from glial cells in the neurons.   In the neurons the glutamine is converted into glutmate with the help of glutaminase enzyme.   Glutamate is stored in the synaptic vesicles.   From synaptic vesicles glutamate release by the process of exocytosis which is Ca⁺ dependent.

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GLUTAMATE SYNTHESIS

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Glutamate Receptors Glutamate receptors are synaptic receptors located primarily on the membranes of neuronal cells. Glutamate ( glutamic acid) is abundant in the human body, but particularly in the nervous system and especially prominent in the human brain where it is the body's most prominent neurotransmitter, the brain's main excitatory neurotransmitter, and also the precursor for GABA, the brain's main inhibitory neurotransmitter. Glutamate receptors are responsible for the glutamate-mediated postsynaptic excitation of neural cells, and are important for neural communication, memory formation, learning, and regulation.

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Ligand gated non-selective cation channels.   Allows flow of K⁺, Na⁺ and sometimes Ca⁺ in response to glutamate binding.   Ionotropic receptors

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IONOTROPIC GLUTAMATE RECEPTORS AMPA KAINATE NMDA

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The NMDA receptor (NMDAR), a glutamate receptor, which plays role in long term potentiation in learning and memory. The NMDAR is a specific type of ionotropic glutamate receptor. NMDA (N-methyl-D-aspartate) is the name of a selective agonist that binds to NMDA receptors but not to other 'glutamate' receptors. THE NMDA RECEPTOR ( N-methyl-D- aspartate ) Calcium flux through NMDARs is thought to be critical in synaptic plasticity, a cellular mechanism for learning and memory.

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• Aminocyclopropanecarboxylic acid • D- Cycloserine • cis-2,3-Piperidinedicarboxylic acid • L-aspartate • Quinolinate • Homocysterate • D-serine • ACPL • L-alanine • GLYX-13 NMDA receptor agonists Partial agonists • N-Methyl-D-aspartic acid (NMDA) • 3,5-dibromo-L-phenylalanine

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NMDA receptor antagonist • Amantadine • Ketamine • Methoxetamine • Phencyclidine (PCP) • Nitrous oxide • Dextromethorphan and dextrorphan • Memantine • Ethanol • Riluzole • Xenon • HU-211 (also a cannabinoid) • Lead • Conantokins • Huperzine A • Atomoxetine

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AMPA Receptors

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The  α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (also known as AMPA receptor, AMPAR, orquisqualate receptor) is a non-NMDA-type  ionotropic   transmembrane receptor for  glutamate  that mediates fast synaptic  transmission in the central nervous system (CNS). AMPARs are found in many parts of the brain and are the most commonly found receptor in the nervous system.

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Agonists 5-Fluorowillardiine AMPA Domoic acid Quisqualic acid Antagonists CNQX Ethanol Kynurenic acid NBQX Perampanel Tezampanel L- Theanine

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Ca 2+ acts as important secondary messenger activates intracellular cascades. Ca 2+ binds to calmodulin protein which in turn activates protein kinases like CAM Kinase CAM KINASE EFFECTS AMPA RECEPTORS IN TWO WAYS- phosphorylates AMPA receptors already present in dendritic spine membrane increasing their conductance to sodium ions. promotes intracellular AMPA receptors to move to the membrane making more receptors available to stimulate the spine. LONG TERM POTENTIATION

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KAINATE RECEPTORS Physiological studies have been identified both post-and presynaptic roles for kainate receptors- - presynaptic kainate receptor facilitate or reduce the neurotransmission depending on where they are in the brain. - postsynaptic kainate receptors can directly mediate excitatory transmi ss ion. Kainate receptors, or KARs, are ionotropic receptors that respond to the neurotransmitter glutamate .. KARs are less understood than AMPA and NMDA receptors .

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Antagonists CNQX DNQX Ethanol NS102 Kynurenic acid Tezampanel

Physiological/pathological roles:

Physiological/pathological roles AMPA receptors mediate most fast EPSPs in the CNS Kainate receptors Regulation of neuronal excitability epilepsy, excitotoxicity and pain NMDA receptors mediate most fast EPSPs in the CNS Anaesthesia Learning and memory Developmental plasticity Epilepsy Excitotoxicity ( eg stroke) Schizophrenia

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Metabotropic glutamate ( mGlu ) receptors are G-protein coupled receptors activated by glutamate , the major excitatory neurotransmitter of the CNS. METABOTROPIC GLUTAMATE RECEPTORS

G-protein coupled receptors:

g b a G-protein coupled receptors Cell membrane G-protein composed of one alpha, beta, and gamma subunit 2 primary signaling cascades: cAMP or phosphatidylinositol pathways Pathway activated depends on alpha subunit type (G α s , G α i , G α q ) GDP bound to a when inactive g b a GDP

G-protein coupled receptors:

g b a G-protein coupled receptors Cell membrane When a ligand binds, the receptor changes conformation, allowing G-protein to be activated (GDP is exchanged for GTP) G-protein dissociates from receptor then subunits from each other. GDP GTP a GTP

cAMP pathway:

g b a cAMP pathway Cell membrane GDP GTP a GTP G α s binds to Adenylate Cyclase (AC) and stimulates cAMP synthesis from ATP G α i binds to AC and inhibits cAMP synthesis AC AC ATP cAMP

Glutamate Receptors Overview:

Glutamate Receptors Overview

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