Glutamate Receptors

1,772
-1

Published on

Complete description of glutamate receptors

Published in: Health & Medicine
0 Comments
4 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total Views
1,772
On Slideshare
0
From Embeds
0
Number of Embeds
1
Actions
Shares
0
Downloads
144
Comments
0
Likes
4
Embeds 0
No embeds

No notes for slide

Glutamate Receptors

  1. 1. PRESENTATION ON GLUTAMATE RECEPTORS PRESENTED TO PRESENTED BY TALAH JAWAID SIR CHETAN RASTOGI
  2. 2. 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
  3. 3. 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.
  4. 4. GLUTAMATE SYNTHESIS
  5. 5. 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.
  6. 6. Ligand gated non-selective cation channels. Allows flow of K⁺, Na⁺ and sometimes Ca⁺ in response to glutamate binding.
  7. 7. IONOTROPIC GLUTAMATE RECEPTORS AMPA KAINATE NMDA
  8. 8. • 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.
  9. 9. • 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
  10. 10. 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
  11. 11. AMPA Receptors
  12. 12. 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.
  13. 13. Agonists • 5-Fluorowillardiine • AMPA • Domoic acid • Quisqualic acid Antagonists • CNQX • Ethanol • Kynurenic acid • NBQX • Perampanel • Tezampanel • L-Theanine
  14. 14. AMPA receptorsNMDA receptor Na+Na+Na+Na+ Ca2+ synaptic strengthening With low presynaptic activity only some of the AMPA receptors are activated, giving rise to a weak EPSP. Under these circumstances the NMDA receptor is inactive despite binding of glutamate because its channel is blocked by Mg .2+ With high presynaptic activity most of the AMPA receptors are activated and the EPSP is strong. Mg2+ The Ca signal ultimately leads to synaptic strengthening. 2+ The strong EPSP (or back-propagated action potential) lifts the Mg block of the NMDA receptor.2+
  15. 15. Ca2+ acts as important secondary messenger activates intracellular cascades. Ca2+ 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
  16. 16. 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 transmission. Kainate receptors, or KARs, are ionotropic receptors that respond to the neurotransmitter glutamate.. KARs are less understood than AMPA and NMDA receptors.
  17. 17. Antagonists a. CNQX b. DNQX c. Ethanol d. NS102 e. Kynurenic acid f. Tezampanel
  18. 18. 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
  19. 19. Metabotropic glutamate (mGlu) receptors are G- protein coupled receptors activated by glutamate, the major excitatory neurotransmitter of the CNS. METABOTROPIC GLUTAMATE RECEPTORS
  20. 20. 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 • (Gαs, Gαi, Gαq) • GDP bound to a when inactive g b a
  21. 21. 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. GTP a GTP
  22. 22. g b a cAMP pathway Cell membrane GTP a GTP • Gαs binds to Adenylate Cyclase (AC) and stimulates cAMP synthesis from ATP • Gαi binds to AC and inhibits cAMP synthesis
  23. 23. Glutamate Receptors Overview
  1. A particular slide catching your eye?

    Clipping is a handy way to collect important slides you want to go back to later.

×