Glutamate (Metabotropic) Receptors

Metabotropic glutamate receptors (mGlus) are coupled to a variety of second messenger systems via G proteins. To date, eight different mGlu subtypes (mGlu1-8) have been cloned and subsequently expressed in various cell lines. These receptors have been classified into 3 groups based on amino acid sequence similarity, agonist pharmacology and the signal transduction pathways to which they couple.

Targets
Literature
Receptor Data

Group I mGlu receptors (mGlu1 and mGlu5) stimulate inositol phosphate metabolism and mobilization of intracellular Ca2+, whereas group II (mGlu2 and mGlu3) and group III (mGlu4 and mGlu6-8) couple to adenylyl cyclase. In addition to the above groups, a fourth (as yet unassigned) group of metabotropic glutamate receptors which couple to phospholipase D has been reported.

Literature for Glutamate (Metabotropic) Receptors

GPCR

GPCR Product Listing

A collection of over 450 products for G protein-coupled receptors, the listing includes research tools for the study of:

  • Rhodopsin-like Receptors
  • Secretin-like Receptors
  • Glutamate Receptors
  • Frizzled Receptors
  • GPCR Signaling
Pain

Pain Research Product Guide

A collection of over 250 products for pain research, the guide includes research tools for the study of:

  • Nociception
  • Ion Channels
  • G-Protein-Coupled Receptors
  • Intracellular Signaling
Metabotropic Glutamate Receptors

Metabotropic Glutamate Receptors Scientific Review

Written by Francine Acher, this review discusses the pharmacology and therapeutic potential of mGlu receptors, and the compounds acting upon them; compounds available from Tocris are listed.

Addiction

Addiction Poster

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Depression

Depression Poster

Major depressive disorder is characterized by depressed mood and a loss of interest and/or pleasure. Updated in 2015 this poster highlights presynaptic and postsynaptic targets for the potential treatment of major depressive disorder, as well as outlining the pharmacology of currently approved antidepressant drugs.

Learning & Memory

Learning & Memory Poster

Recognition memory enables us to make judgements about whether or not we have encountered a particular stimulus before. This poster outlines the cellular mechanisms underlying recognition memory and its links to long-term depression, as well as the use of pharmacological intervention to assess the role of neurotransmitters in recognition memory.

Parkinson's

Parkinson's Poster

Parkinson's disease (PD) causes chronic disability and is the second most common neurodegenerative condition. This poster outlines the neurobiology of the disease, as well as highlighting current therapeutic treatments for symptomatic PD, and emerging therapeutic strategies to delay PD onset and progression.

Metabotropic Glutamate Receptor Data

Receptor Subtype Group I Group II Group III PLD Coupled mGlu Receptor
Subtypes mGlu1
mGlu5
mGlu2
mGlu3
mGlu4
mGlu6
mGlu7
mGlu8
Undetermined
Transduction Mechanism ↑ PLC ↓ AC ↓ AC ↑ PLD
Example Agonists L-Quisqualic acid (0188)
(S)-3,5-DHPG (0805)
CHPG (1049)
DCG-IV (0975)
L-CCG-I (0333)
(2R,4S)-APDC (1208)
LY 379268 (2453)
LY 354740 (3246)
L-AP4 (0103)
(S-3,4-DCPG (1302)
ACPT I (1111)
(RS)-PPG (1220)
VU 0155041 (3248)
L-CSA (0216)
Example Antagonists CPCCOEt (1028)
AIDA (0904)
Fenobam (2386)
MPEP (1212)
LY 367385 (1237)
YM 298198 (2448)
(RS)-APICA (1073)
EGLU (0971)
LY 341495 (1209)
CPPG (0972)
MAP4 (0711)
MSOP (0803)
UBP 1112 (1369)
MMPIP (2963)
(RS)-3,5-DHPG (0342)

Properties of Selected Metabotropic Glutamate Receptor Antagonists

Group I

Antagonist mGlu1a mGlu5a mGlu2 mGlu3 mGlu4 mGlu6 mGlu7 mGlu8
(S)-MCPG (0337) 124-543 (Kb) 154-460 (Kb)
> 2000 (Kb)
15 (Ki) 317 (Ki) > 1000 (IC50) > 100 (IC50) > 1000 (IC50) 320 (IC50)
(S)-4CPG (0323) 15-182 (Kb) > 1000 (Kb)
145 (Kb)
> 300 (Kb)
366 (Ki)
Weak agonist
ND > 1000 (IC50) Weak agonist ND Agonist
(S)-4C3HPG (0320) 11.5-393 (Kb) 157 (Kb)
Agonist ND > 1000 (IC50) ND ND Agonist
AIDA (0904) 3.4 (pKb) > 1000 (IC50) Weak agonist ND > 1000 (IC50) ND ND ND
CPCCOEt (1028) 4.76 (pKb) > 100 (IC50) > 100 (IC50) ND > 100 (IC50) ND > 100 (IC50) > 100 (IC50)
MPEP (1212) > 100 (IC50) 0.032 (IC50) > 100 (IC50) ND > 100 (IC50) > 100 (IC50) > 100 (IC50) ND
SIB 1757 (1215) > 1000 (IC50) 0.4 (IC50 > 30 (IC50) ND > 30 (IC50) > 30 (IC50) > 30 (IC50) > 30 (IC50)
SIB 1893 (1214) > 30 (IC50) 0.3 (IC50) > 30 (IC50) ND > 30 (IC50) > 30 (IC50) > 30 (IC50) > 30 (IC50)
LY 367385 (1237) 8.8 (IC50) > 100 (IC50) ND ND ND ND ND ND
3-MATIDA (2196) 6.3 (IC50) > 300 (IC50) > 300 (IC50) ND > 300 (IC50) ND ND ND

Group II and III

Antagonist mGlu1a mGlu5a mGlu2 mGlu3 mGlu4 mGlu6 mGlu7 mGlu8
MPPG (0853) 1100 (IC50) No effect 12 (Ki) ND 22 (KD) 138 (Kb) ND 20 (IC50)
MAP4 (0711) No effect ND 15 (Ki)
Weak agonist
ND 36 (KD)
190 (Ki)
Weak moderate agonist ND 25 (IC50)
DCG IV (0975) 389 (IC50) 630 (IC50)
Agonist Agonist 22.5 (IC50) 39.6 (IC50) 40.1 (IC50) 32 (IC50)
ACPT-II (1112) 115 (Kb) ND 88 (Kb) ND 77 (Kb) ND ND 123 (IC50)
LY 341495 (1209) 6.8 (IC50) 8.2 (IC50) 0.002 (Ki) 0.001 (Ki) 22 (IC50) ND 0.99 (IC50) 0.173 (IC50)

References

Doherty et al (1999) Br.J.Pharmacol. 126 205. Lin et al (1997) Neuropharmacology 36 917. Brabet et al (1995) Neuropharmacology 34 895. Cartmell et al (1998) Br.J.Pharmacol. 123 497. Laurie et al (1995) Naunyn-Schmied.Arch.Pharmacol. 351 565. Hayashi et al (1994) J.Neurosci. 14 3370. Laurie et al (1997) Neuropharmacology 36 145. Saugstad et al (1994) Mol.Pharmacol. 45 367. Saugstad et al (1997) Mol.Pharmacol. 51 119. Thomsen et al (1994) Eur.J.Pharmacol.Mol.Pharmacol.Sect. 267 77. De Colle et al (2000) Eur.J.Pharmacol. 394 17. Kingston et al (1995) Neuropharmacology 34 887. Bräuner-Osborne et al (1998) Eur.J.Pharmacol. 350 311. Hermans et al (1999) Br.J.Pharmacol. 126 873. Moroni et al (1997) J.Pharmacol.Exp.Ther. 281 721. Hermans et al (1998) Neuropharmacology 37 1645. Litschig et al (1999) Mol.Pharmacol. 55 453. Gasparini et al (1999) Neuropharmacology 38 1493. Varney et al (1999) J.Pharmacol.Exp.Ther. 290 170. Thomsen et al (1996) Mol.Pharmacol. 50 6. Kowal et al (1998) Soc.Neurosci.Abstr. 24 576. Abe et al (1992) J.Biol.Chem. 267 13361. Sekiyama et al (1996) Br.J.Pharmacol. 117 1493. Brabet et al (1998) Neuropharmacology 37 1043. Acher et al (1997) J.Med.Chem. 40 3119. Clark et al (1997) Bioorg.Med.Chem. 7 2777. Johnson et al (1999) Neuropharmacology 38 1519. Moroni et al (2002) Neuropharmacology 42 741.