For the best experience on the Abcam website please upgrade to a modern browser such as Google Chrome

We use cookies to make our site as useful as possible.

Our Cookie Policy explains how you can opt-out of the cookies we use.

If you continue without changing your cookie settings, we'll assume you’re happy with this.

Continue Continue

United States
Your country/region is currently set to:

If incorrect, please enter your country/region into the box below, to view site information related to your country/region.

Call (888) 77-ABCAM (22226) or contact us
Need help? Contact us

  • My account
  • Sign out
Sign in or Register with us

Welcome

Sign in or

Don't have an account?

Register with us
My basket
Quick order
Abcam homepage

  • Research Products
    By product type
    Primary antibodies
    Secondary antibodies
    ELISA and Matched Antibody Pair Kits
    Cell and tissue imaging tools
    Cellular and biochemical assays
    Proteins and Peptides
    By product type
    Proteomics tools
    Agonists, activators, antagonists and inhibitors
    Cell lines and Lysates
    Multiplex miRNA assays
    Multiplex Assays
    By research area
    Cancer
    Cardiovascular
    Cell Biology
    Epigenetics
    Metabolism
    Developmental Biology
    By research area
    Immunology
    Microbiology
    Neuroscience
    Signal Transduction
    Stem Cells
  • Diagnostic & Therapeutic Solutions
    Custom solutions & partnerships

    Custom antibody development and commercial partnerships to advance your diagnostic and therapeutic discovery.

    Create custom solutions with us

    Partner with us

  • Support
    Support hub

    Access advice and support for any research roadblock

    View support hub

    Protocols

    Your experiments laid out step by step

    View protocols

  • Events
    • Conference calendar
    • Cancer
    • Cardiovascular
    • Epigenetics & Nuclear signaling
    • Immunology
    • Neuroscience
    • Stem cells
    • Tradeshows
    • Scientific webinars
    Keep up to date with the latest events

    Full event breakdown with abstracts, speakers, registration and more

    View global event calendar

  • Pathways
    Cell signalling pathways

    View all pathways

    View all interactive pathways

Supporting our customers and employees during the COVID-19 pandemic. Read more

Metabotropic glutamate receptors

Related

  • Ionotropic glutamate receptors

    Overview of the structure and function of metabotropic glutamate receptors

    ​Metabotropic glutamate receptors (mGluRs) are class C, G-protein-coupled receptors (GPCRs) in the CNS that play a role in modulating synaptic transmission and neuronal excitability. 

    Contents

    • Introduction to metabotropic glutamate receptors
    • Structure of metabotropic glutamate receptors
    • Metabotropic glutamate receptors groups and function

    See our full guide to glutamate receptors

    Introduction to metabotropic glutamate receptors

    ​​​Metabotropic glutamate receptors provide a mechanism through which glutamate can modulate cell excitability and synaptic transmission via second messenger signaling pathways. These receptors lack ion channels, and instead affect other channels through the activation of intermediate molecules called G-proteins1. 

    Metabotropic gluatmate receptors are divided into three groups based on their sequence similarity, pharmacology and signaling mechanisms: group I (mGlu1 and mGlu5 receptors), Group II (mGlu2 and mGlu3 receptors) and Group III (mGlu4, mGlu6, mGlu7 and mGlu8 receptors)2.

    ​

    ​Figure 1: Metabotropic glumatate receptor groups.
    ​

    Structure of metabotropic glutamate receptors

    mGluRs consist of seven transmembrane-spanning domains, an extracellular N-terminal domain and an intracellular C-terminus. The N-terminal domain is formed by a pair of hinged domains, termed the Venus fly-trap domain, and is responsible for binding glutamate and activating the receptor3. The C-terminal is important in modulating G-protein-coupling (Figure 2).

    Metabotropic glutamate receptor

    Figure 2: Schematic structure of the metabotropic glutamate receptors. (Adapted from Kenny, P.J. & Markou, 2004)

    ​

    Metabotropic glutamate receptors groups and functions

    ​mGluRs function as neuromodulators that can modulate neuronal excitability or neurotransmitter release1,4. In general, Group I mGluRs increase neuron excitability, whereas Groups II and III tend to suppress neuronal excitability5. Group I mGluRs are coupled to Gαq proteins, and activate phospholipase C1. Groups II and III receptors are coupled to Gi/o proteins, leading to adenylyl cyclase inhibition and cAMP formation, limiting downstream protein kinase A (PKA) activation1.

    Group I: mGlu1 and mGlu5 

    Group I mGluRs are primarily located postsynaptically and function by stimulating phospholipase C (PLC) to increase levels of diacylglycerol and inositol triphosphate. This activates protein kinase C (PKC) and the release of intracellular Ca2+, ultimately inhibiting presynaptic K+ channels and delaying nerve terminal repolarization. Group I mGluRs can also activate a range of downstream effectors, which may be important in the regulation of synaptic plasticity1. 

    mGlu5 receptors are an interesting therapeutic target for negative allosteric modulators as a potential therapy for depression, fragile X syndrome, anxiety, obsessive-compulsive disorders, and levodopa-induced dyskinesia in Parkinson's disease6.

    Group II: mGlu2 and mGlu3

    Group II mGluRs function presynaptically to suppress neuronal excitability through the inhibition of adenylate cyclase5. mGlu2 and mGlu3 subtypes share a high degree of sequence similarity and are highly expressed in the hippocampus, cortex, nucleus accumbens, striatum and amygdala7. These receptors are potential novel targets in the treatment of anxiety disorders and schizophrenia8–10.​

    Group I mGluRs are primarily located postsynaptically and function by stimulating phospholipase C (PLC) to increase levels of diacylglycerol and inositol triphosphate. This activates protein kinase C (PKC) and the release of intracellular Ca2+, ultimately inhibiting presynaptic K+ channels and delaying nerve terminal repolarization. Group I mGluRs can also activate a range of downstream effectors, which may be important in the regulation of synaptic plasticity1. 

    mGlu5 receptors are an interesting therapeutic target for negative allosteric modulators as a potential therapy for depression, fragile X syndrome, anxiety, obsessive-compulsive disorders, and levodopa-induced dyskinesia in Parkinson's disease6.

    ​Group III: mGlu4, mGlu6, mGlu7 and mGlu8

    Group III mGluRs function in the same manner as Group II, being expressed presynaptically and suppressing neuronal excitability by inhibiting adenylate cyclase5. mGlu4 and mGlu7 receptors are widely distributed in the brain7, mGlu6 receptors are localized to the retina11, and mGlu8 receptors are primarily found at low levels in the hippocampus, hypothalamus and olfactory bulb7. Group III mGluRs play a role in synaptic remodeling and persistent drug seeking and addiction, exerting their effect via an as yet undefined presynaptic mechanism – possibly also extending to postsynaptic modulation12.

    Related products

    • > ​​mGluR agonists and antagonists
    • > Anti-mGluR primary antibodies​
    • > mGluR proteins and peptides

    ​
    ​References

    1. Niswender, C. M. & Conn, P. J. Metabotropic Glutamate Receptors: Physiology, Pharmacology, and Disease. Annu Rev Pharmacol Toxicol 50, 295–322 (2010).

    2. Alexander, S. P. H. et al. The Concise Guide to Pharmacology 2013/14: G protein-coupled receptors. Br. J. Pharmacol. 170, 1459–581 (2013).

    3. Pin, J. P., Galvez, T. & Prézeau, L. Evolution, structure, and activation mechanism of family 3/C G-protein-coupled receptors. Pharmacol. Ther. 98, 325–354 (2003).

    4. Pinheiro, P. S. & Mulle, C. Presynaptic glutamate receptors: physiological functions and mechanisms of action. Nat. Rev. Neurosci. 9, 423–436 (2008).

    5. Pin, J.-P. et al. Metabotropic glutamate receptors, introduction. IUPHAR/BPS Guide to PHARMACOLOGY (2015). at 

    6. Jaeschke, G. et al. Metabotropic glutamate receptor 5 negative allosteric modulators: discovery of 2-chloro-4-[1-(4-fluorophenyl)-2,5-dimethyl-1H-imidazol-4-ylethynyl]pyridine (basimglurant, RO4917523), a promising novel medicine for psychiatric diseases. J. Med. Chem. 58, 1358–71 (2015).

    7. Hovelsø, N. et al. Therapeutic potential of metabotropic glutamate receptor modulators. Curr. Neuropharmacol. 10, 12–48 (2012).

    8. Swanson, C. J. et al. Metabotropic glutamate receptors as novel targets for anxiety and stress disorders. Nat. Rev. Drug Discov. 4, 131–144 (2005).

    9. Conn, P. J., Lindsley, C. W. & Jones, C. K. Activation of metabotropic glutamate receptors as a novel approach for the treatment of schizophrenia. Trends Pharmacol. Sci. 30, 25–31 (2009).

    10. Patil, S. T. et al. Activation of mGlu2/3 receptors as a new approach to treat schizophrenia: a randomized Phase 2 clinical trial. Nat. Med. 13, 1102–7 (2007).

    11. Nakajima, Y. et al. Molecular characterization of a novel retinal metabotropic glutamate receptor mGluR6 with a high agonist selectivity for L-2-amino-4- phosphonobutyrate. J. Biol. Chem. 268, 11868–11873 (1993).

    12. Mao, L., Guo, M., Jin, D., Xue, B. & Wang, J. Q. Group III metabotropic glutamate receptors and drug addiction. Front. Med. 7, 445–451 (2013).

    13. Kenny, P. J. & Markou, A. The ups and downs of addiction: Role of metabotropic glutamate receptors. Trends Pharmacol. Sci. 25, 265–272 (2004).











    Get resources and offers direct to your inbox Sign up
    A-Z by research area
    • Cancer
    • Cardiovascular
    • Cell biology
    • Developmental biology
    • Epigenetics & Nuclear signaling
    • Immunology
    • Metabolism
    • Microbiology
    • Neuroscience
    • Signal transduction
    • Stem cells
    A-Z by product type
    • Primary antibodies
    • Secondary antibodies
    • Biochemicals
    • Isotype controls
    • Flow cytometry multi-color selector
    • Kits
    • Loading controls
    • Lysates
    • Peptides
    • Proteins
    • Slides
    • Tags and cell markers
    • Tools & Reagents
    Help & support
    • Support
    • Make an Inquiry
    • Protocols & troubleshooting
    • Placing an order
    • RabMAb products
    • Biochemical product FAQs
    • Training
    • Browse by Target
    Company
    • Corporate site
    • Investor relations
    • Company news
    • Careers
    • About us
    • Blog
    Events
    • Tradeshows
    • Conferences
    International websites
    • abcam.cn
    • abcam.co.jp

    Join with us

    • LinkedIn
    • facebook
    • Twitter
    • YouTube
    • Terms of sale
    • Website terms of use
    • Cookie policy
    • Privacy policy
    • Legal
    • Modern slavery statement
    © 1998-2021 Abcam plc. All rights reserved.