Metabotropic Glutamate Receptors


The metabotropic glutamate receptors are a family of G protein‐coupled receptors widely distributed in the central nervous system, acting to modulate synaptic function through interactions with other receptors, signalling mechanisms and (potentially) gene expression.

Keywords: metabotropic glutamate receptor; mGluR; excitory amino acid; LTP; LTD

Figure 1.

Comparison of the structures of the metabotropic glutamate (mGlu) receptor, mGlu, and the β2‐adrenergic receptor. Schematic representations of the structure of these receptors as representatives of their respective superfamilies are presented. The locations of the ligand‐binding domains and the G protein‐coupling sites are indicated, as is the region of the mGlu receptor containing the Homer‐binding domain and the calmodulin‐binding domains in other subtypes. Also indicated on the mGlu receptor are the locations of mutations S165 and T188 (marked with an X) that reduce the affinity of the receptor for glutamate.

Figure 2.

Dendrogram of the cloned members of the metabotropic glutamate (mGlu) receptor family. The diagram represents the sequence homology between members of the mGlu receptor family. The receptors are subdivided into the three groups on the basis of sequence homology, signal transduction mechanism (+ PLC, stimulation of phospholipase C; −AC, inhibition of adenylyl cyclase) in heterologous expression systems, and pharmacology.



Bortolotto ZA, Bashir ZI, Davies CH and Collingridge GL (1994) Metabotropic glutamate receptors activate a molecular switch which regulates the induction of long‐term potentiation. Nature 368: 740–743.

Chen Y, Bacon G, Sher E et al. (2000) Evaluation of the activity of a novel metabotropic glutamate receptor antagonist (+/−)‐2‐amino‐2‐(3‐cis and trans‐carboxycyclobutyl‐3‐(9‐thioxanthyl)propionic acid) in the in vitro neonatal spinal cord and in an in vivo pain model. Neuroscience 95: 787–793.

Conn PJ and Pin J‐P (1997) Pharmacology and functions of metabotropic glutamate receptors. Annual Review of Pharmacology and Toxicology 37: 205–237.

Fitzjohn SM, Bortolotto ZA, Palmer MJ et al. (1998) The potent mGlu receptor antagonist LY341495 identifies roles for both cloned and novel mGlu receptors in hippocampal synaptic plasticity. Neuropharmacology 37: 1445–1458.

Harvey J and Collingridge GL (1993) Signal transduction pathways involved in the acute potentiation of NMDA responses by 1S,3R‐ACPD in rat hippocampal slices. British Journal of Pharmacology 109: 1085–1090.

Helton DR, Tizzano JP, Monn JA, Schoepp DD and Kallman MJ (1998) Anxiolytic and side‐effect profile of LY354740: a potent, highly selective, orally active agonist for group II metabotropic glutamate receptors. Journal of Pharmacology and Experimental Therapeutics 284: 651–660.

Jia Z, Lu Y, Henderson J et al. (1998) Selective abolition of the NMDA component of long‐term potentiation in mice lacking mGluR5. Learning and Memory 5: 331–343.

Kingston AE, O’Nell MJ, Bond A et al. (1999) Neuroprotective actions of novel and potent ligands of group I and group II metabotropic glutamate receptors. New York Academy of Sciences 890: 438–449.

Nakahara K, Okada M and Nakanishi S (1997) The metabotropic glutamate receptor mGluR5 induces calcium oscillations in cultured astrocytes via protein kinase C phosphorylation. Journal of Neurochemistry 69: 1467–1475.

Tu JC, Xiao B, Yuan JP et al. (1998) Homer binds a novel proline‐rich motif and links group 1 metabotropic glutamate receptors with IP3 receptors. Neuron 21: 717–726.

Further Reading

Anwyl R (1999) Metabotropic glutamate receptors: electrophysiological properties and role in plasticity. Brain Research. Brain Research Reviews 29: 83–120.

Bortolotto ZA, Fitzjohn SM and Collingridge GL (1999) Roles of metabotropic glutamate receptors in LTP and LTD in the hippocampus. Current Opinion in Neurobiology 9: 299–304.

Moroni F, Nicoletti F and Pellegrini‐Giampietro DE (eds) (1998) Metabotropic Glutamate Receptors and Brain Function. London: Portland Press.

Schoepp DD, Jane DE and Monn JA (1999) Pharmacological agents acting at subtypes of glutamate receptors. Neuropharmacology 38: 1431–1476.

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How to Cite close
Doherty, AJ, and Collingridge, GL(Apr 2001) Metabotropic Glutamate Receptors. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0000237]