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mGlu4 receptor

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Target id: 292

Nomenclature: mGlu4 receptor

Family: Metabotropic glutamate receptors

Contents:

Gene and Protein Information Click here for help
class C G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 912 6p21.31 GRM4 glutamate metabotropic receptor 4 17,35,41,62-63
Mouse 7 912 17 A3.3 Grm4 glutamate receptor, metabotropic 4
Rat 7 912 20p12 Grm4 glutamate metabotropic receptor 4 39,50
Gene and Protein Information Comments
The mouse sequence is provisional and has not been confirmed.
Previous and Unofficial Names Click here for help
mGluR4 | GPRC1D | glutamate receptor
Database Links Click here for help
Specialist databases
GPCRdb grm4_human (Hs), grm4_mouse (Mm), grm4_rat (Rn)
Other databases
Alphafold Q14833 (Hs), Q68EF4 (Mm), P31423 (Rn)
ChEMBL Target CHEMBL2736 (Hs), CHEMBL4105794 (Mm), CHEMBL2787 (Rn)
Ensembl Gene ENSG00000124493 (Hs), ENSMUSG00000063239 (Mm), ENSRNOG00000000487 (Rn)
Entrez Gene 2914 (Hs), 268934 (Mm), 24417 (Rn)
Human Protein Atlas ENSG00000124493 (Hs)
KEGG Gene hsa:2914 (Hs), mmu:268934 (Mm), rno:24417 (Rn)
OMIM 604100 (Hs)
Pharos Q14833 (Hs)
RefSeq Nucleotide NM_000841 (Hs), NM_001013385 (Mm), NM_022666 (Rn)
RefSeq Protein NP_000832 (Hs), NP_001013403 (Mm), NP_073157 (Rn)
UniProtKB Q14833 (Hs), Q68EF4 (Mm), P31423 (Rn)
Wikipedia GRM4 (Hs)
Natural/Endogenous Ligands Click here for help
L-glutamic acid
L-serine-O-phosphate
Comments: Other endogenous ligands include L-aspartic acid, L-serine-O-phosphate, NAAG and L-cysteine sulphinic acid

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[3H]AP4 Small molecule or natural product Ligand is labelled Ligand is radioactive Ligand has a PDB structure Rn Full agonist 6.3 pKd 23
⤷ pKd 6.3 [23]
L-glutamic acid Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Rn Full agonist 4.9 – 5.5 pKi 2,23,53-54
⤷ pKi 4.9 – 5.5 [2,23,53-54]
FP0429 Small molecule or natural product Hs Full agonist 7.3 – 7.4 pEC50 18
⤷ pEC50 7.3 – 7.4 [18]
LSP4-2022 Small molecule or natural product Click here for species-specific activity table Hs Agonist 7.0 pEC50 22
⤷ pEC50 7.0 (EC50 1.1x10-7 M) [22]
L-AP4 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Agonist 6.5 pEC50 63
⤷ pEC50 6.5 (EC50 3.2x10-7 M) [63]
L-serine-O-phosphate Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Agonist 5.9 pEC50 63
⤷ pEC50 5.9 (EC50 1.42x10-6 M) [63]
LSP1-2111 Small molecule or natural product Click here for species-specific activity table Rn Agonist 5.7 pEC50 6
⤷ pEC50 5.7 (EC50 2.2x10-6 M) [6]
(R,S)-4-PPG Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.3 pEC50 19-20
⤷ pEC50 5.3 [19-20]
L-glutamic acid Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Agonist 4.7 – 5.5 pEC50 44
⤷ pEC50 4.7 – 5.5 [44]
(S)-3,4-DCPG Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 5.1 pEC50 52
⤷ pEC50 5.1 [52]
ACPT-I Small molecule or natural product Click here for species-specific activity table Rn Full agonist 5.1 pEC50 1
⤷ pEC50 5.1 [1]
L-AP4 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Rn Full agonist 6.0 – 6.4 pIC50 16,23,51,54
⤷ pIC50 6.0 – 6.4 [16,23,51,54]
L-serine-O-phosphate Small molecule or natural product Ligand is endogenous in the given species Ligand has a PDB structure Rn Full agonist 5.4 – 6.2 pIC50 16,23,51,54-55
⤷ pIC50 5.4 – 6.2 [16,23,51,54-55]
L-CCG-I Small molecule or natural product Click here for species-specific activity table Rn Full agonist 4.3 – 5.0 pIC50 25
⤷ pIC50 4.3 – 5.0 [25]
View species-specific agonist tables
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
CPPG Small molecule or natural product Click here for species-specific activity table Rn Antagonist 4.6 pKi 23
⤷ pKi 4.6 [23]
MAP4 Small molecule or natural product Click here for species-specific activity table Rn Antagonist 4.6 pKi 23
⤷ pKi 4.6 [23]
MPPG Small molecule or natural product Rn Antagonist 4.2 pKi 23
⤷ pKi 4.2 [23]
LY341495 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 4.7 pIC50 30
⤷ pIC50 4.7 [30]
View species-specific antagonist tables
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
ADX88178 Small molecule or natural product Ligand has a PDB structure Hs Positive 7.4 pKi 33
⤷ pKi 7.4 (Ki 3.9x10-8 M) [33]
ADX88178 Small molecule or natural product Ligand has a PDB structure Hs Positive 8.5 pEC50 33
⤷ pEC50 8.5 (EC50 3.5x10-9 M) [33]
compound 22a [PMID: 21688779] Small molecule or natural product Hs Positive 8.1 pEC50 26
⤷ pEC50 8.1 (EC50 9x10-9 M) [26]
ADX88178 Small molecule or natural product Ligand has a PDB structure Rn Positive 8.0 pEC50 33
⤷ pEC50 8.0 (EC50 9.1x10-9 M) [33]
VU2957 Small molecule or natural product Primary target of this compound Hs Positive 7.2 pEC50 42
⤷ pEC50 7.2 (EC50 6.44x10-8 M) [42]
foliglurax Small molecule or natural product Hs Positive 7.1 pEC50 10
⤷ pEC50 7.1 (EC50 7.6x10-8 M) [10]
Description: Calcium assay using human mGluR4.
compound 1 [PMID: 22465637] Small molecule or natural product Hs Positive 6.7 pEC50 27
⤷ pEC50 6.7 (EC50 2.2x10-7 M) [27]
VU0361737 Small molecule or natural product Hs Positive 6.6 pEC50 15
⤷ pEC50 6.6 (EC50 2.4x10-7 M) [15]
SIB-1893 Small molecule or natural product Click here for species-specific activity table Hs Positive 6.3 – 6.8 pEC50 36
⤷ pEC50 6.3 – 6.8 (EC50 4.7x10-7 – 1.5x10-7 M) obtained in the presence of L-AP4 [36]
VU0400195 Small molecule or natural product Hs Positive 6.5 pEC50 29
⤷ pEC50 6.5 (EC50 2.91x10-7 M) [29]
VU0364770 Small molecule or natural product Ligand has a PDB structure Rn Positive 6.5 pEC50 28
⤷ pEC50 6.5 (EC50 2.9x10-7 M) [28]
MPEP Small molecule or natural product Click here for species-specific activity table Hs Positive 6.3 – 6.6 pEC50 36
⤷ pEC50 6.3 – 6.6 (EC50 5.5x10-7 – 2.6x10-7 M) obtained in the presence of L-AP4 [36]
VU0359516 Small molecule or natural product Hs Positive 6.4 pEC50 61
⤷ pEC50 6.4 (EC50 3.8x10-7 M) [61]
VU0400195 Small molecule or natural product Rn Positive 6.4 pEC50 29
⤷ pEC50 6.4 (EC50 3.76x10-7 M) [29]
Lu AF21934 Small molecule or natural product Hs Positive 6.3 pEC50 5
⤷ pEC50 6.3 (EC50 5x10-7 M) [5]
VU0001171 Small molecule or natural product Hs Positive 6.2 pEC50 60
⤷ pEC50 6.2 (EC50 6.5x10-7 M) [60]
VU0155041 Small molecule or natural product Hs Positive 6.1 pEC50 37
⤷ pEC50 6.1 (EC50 7.98x10-7 M) [37]
compound 7 [PMID: 20638279] Small molecule or natural product Hs Positive 6.0 pEC50 14
⤷ pEC50 6.0 (EC50 1x10-6 M) [14]
VU0364770 Small molecule or natural product Ligand has a PDB structure Hs Positive 6.0 pEC50 28
⤷ pEC50 6.0 (EC50 1.1x10-6 M) [28]
compound 11 [PMID: 20638279] Small molecule or natural product Hs Positive 6.0 pEC50 14
⤷ pEC50 6.0 (EC50 1x10-6 M) [14]
VU0092145 Small molecule or natural product Hs Positive 5.5 – 5.7 pEC50 60
⤷ pEC50 5.5 – 5.7 (EC50 3x10-6 – 1.8x10-6 M) [60]
VU0080241 Small molecule or natural product Hs Positive 5.3 pEC50 38
⤷ pEC50 5.3 (EC50 4.6x10-6 M) [38]
PHCCC Small molecule or natural product Click here for species-specific activity table Hs Positive 4.5 pEC50 34
⤷ pEC50 4.5 obtained in the presence of L-AP4 [34]
View species-specific allosteric modulator tables
Allosteric Modulator Comments
pEC50 values for MPEP and SIB-1893 were obtained in the presence of L-AP4 [36]. 4-PAM2 was reported in [33] as a radioligand, but no affinity was given.
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Adenylyl cyclase inhibition
References:  45,47
Tissue Distribution Click here for help
Testes.
Species:  Human
Technique:  RT-PCR.
References:  49
CNS: cerebellar cortex, globus pallidus, ventral pallidum > olfactory tubercle, striatum, entopeduncular nucleus, sensory relay nuclei of the thalamus, medial and dorsolateral geniculate nuclei, substantia nigra, spinal trigeminal nucleus > neocortex layers I-III and V, piriform cortex, hippocampus, lateral and basolateral amygdaloid nuclei, superficial grey of the superior colliculus.
Species:  Mouse
Technique:  immunocytochemistry.
References:  13
CNS: cerebellum, globus pallidus > substantia nigra pars reticulata, entopeduncular nucleus, striatum, hippocampus, neocortex, thalamus.
Species:  Mouse
Technique:  immunocytochemistry.
References:  9
Presynaptic active zone of excitatory axon terminals.
Species:  Rat
Technique:  immunocytochemistry.
References:  13
CNS: cerebellar cortex, main olfactory bulb, medial septal nucleus, mammillary nuclei > accessory olfactory bulb, olfactory tubercle, subthalamic nucleus, thalamus, pontine nuclei > neocortex, hippocampus, bed nucleus of the stria terminalis, basolateral amygdaloid nucleus, striatum, nuclues accumbens, interpeduncular nucleus, superior collicus, red nucleus, oculomotor nucleus, trochlear nucleus, periacqueductal gray.
Species:  Rat
Technique:  in situ hybridisation.
References:  40
Pancreatic islets of Langerhans (alpha and F cells).
Species:  Rat
Technique:  RT-PCR.
References:  57
Presynaptic active zone of GABAergic axon terminals.
Species:  Rat
Technique:  immunocytochemistry.
References:  9,31
Taste buds.
Species:  Rat
Technique:  in situ hybridisation.
References:  11-12,56
Retina.
Species:  Rat
Technique:  in situ hybridisation.
References:  24
Retina (cell bodies of ganglion cells).
Species:  Rat
Technique:  Northern Blotting and in situ hybridisation.
References:  3
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays Click here for help
Measurement of intracellular calcium levels in HEK cells transfected with the rat mGlu4 receptor and G15 and loaded with a calcium-sensitive dye, Fluo-4 (see comments).
Species:  Rat
Tissue:  HEK cells.
Response measured:  L-AP4-induced release of intracellular calcium.
References:  46
Measurement of intracellular calcium levels in CHO cells transfected with the human mGlu4 receptor as well as a promiscuous/chimeric G-protein comprising Gq with five amino acids from the C-terminal replaced with those from Gi3.
The calcium-mobilization assays are compatible with the fluorometric imaging plate reader formats.
Species:  Human
Tissue:  CHO cells.
Response measured:  Mobilisation of intracellular calcium.
References:  32
Measurement of cAMP levels in CHO cells transfected with the rat mGlu4 receptor.
Species:  Rat
Tissue:  CHO cells
Response measured:  Inhibition of cAMP production.
References:  51
Measurement of IP levels in HEK 293 cells transfected with the rat mGlu4 receptor and the chimeric G-protein Gqi9.
Species:  Rat
Tissue:  HEK 293 cells,
Response measured:  Stimulation of IP production.
References:  8
Functional Assay Comments
Functional responses for a series of chimeras between mGlu4/mGlu6 and mGlu4/mGlu7 led to the identification of key amino acid residues that elucidate the disperson of agonist affinities for the group III receptors mGlu4, mGluR6 and mGlu7.
Physiological Functions Click here for help
In addition to the taste-mGlu4 receptor, brain-mGlu4 may be important for the sensation of glutamate taste ("umami") in rat tongue.
Species:  Rat
Tissue:  Tongue
References:  11-12,56
Conditioned taste aversion (CTA) experiments were performed to show that L-AP4 (mGlu4 agonist) mimics the taste of monosodium glutamate (MSG) ("umami" taste sense) on the rat tongue.
Species:  Rat
Tissue:  In vivo.
References:  12
Physiological Consequences of Altering Gene Expression Click here for help
It was found that mGlu4 knockout mice had altered spatial learning and memory when compared against wild-type mice. These knockout mise also displaced a resistance to chemically-induced absence seizures likely mediated by alterations in glutamamte and GABA release in the thalamus. The mGlu4 knockout mice also do not show the motor stimulatory effect of ethanol.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  7,21,48,59
It was shown that mGlu4 knockout mice, while having normal spontaneous motor activities, were deficient in learning complex motor tasks.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  43
Agonists of mGlu4 modulate excitatory transmission in dopamine neurons and reduce neuronal degeneration in rodent Parkinsonian models.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  4,58
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Grm4tm1Hpn Grm4tm1Hpn/Grm4tm1Hpn
involves: 129S1/Sv * 129X1/SvJ * CD-1		 MGI:1351341  MP:0002804 abnormal motor learning PMID: 8815915 
Grm4tm1Hpn Grm4tm1Hpn/Grm4tm1Hpn
involves: 129S1/Sv * 129X1/SvJ * CD-1		 MGI:1351341  MP:0002920 decreased paired-pulse facilitation PMID: 8815915 
Grm4tm1Hpn Grm4tm1Hpn/Grm4tm1Hpn
involves: 129S1/Sv * 129X1/SvJ * CD-1		 MGI:1351341  MP:0002922 decreased post-tetanic potentiation PMID: 8815915 
Biologically Significant Variants Click here for help
Type:  Naturally occurring mutation
Species:  Rat
Description:  A truncated form of the mGlu4 receptor, taste-mGlu4, which lacks approximately 50% of the extracellular amino terminus of the full-length mGlu4 receptor, was found to impart glutamate taste ("umami") in rat taste buds. As for the mGlu4(b) variant, there is no strong data supporting the existence of this variant.
References:  11-12
Type:  Splice variant
Species:  Rat
Description:  A variant of mGlu4(a), called mGlu4(b) has been reported that would have 135 different residues replacing the entire C-terminal tail of mGlu4(a). However, the existence of this variant has not been confirmed by RT-PCR analysis, and the human genome sequence did not reveal the presence of consensus donor and acceptor splice sites possibly responsible for the generation of this mGlu4(b) variant.
References:  13,54

References

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1. Acher FC, Tellier FJ, Azerad R, Brabet IN, Fagni L, Pin JP. (1997) Synthesis and pharmacological characterization of aminocyclopentanetricarboxylic acids: new tools to discriminate between metabotropic glutamate receptor subtypes. J Med Chem, 40 (19): 3119-29. [PMID:9301676]

2. Ahmadian H, Nielsen B, Bräuner-Osborne H, Johansen TN, Stensbøl TB, Sløk FA, Sekiyama N, Nakanishi S, Krogsgaard-Larsen P, Madsen U. (1997) (S)-homo-AMPA, a specific agonist at the mGlu6 subtype of metabotropic glutamic acid receptors. J Med Chem, 40 (22): 3700-5. [PMID:9357538]

3. Akazawa C, Ohishi H, Nakajima Y, Okamoto N, Shigemoto R, Nakanishi S, Mizuno N. (1994) Expression of mRNAs of L-AP4-sensitive metabotropic glutamate receptors (mGluR4, mGluR6, mGluR7) in the rat retina. Neurosci Lett, 171 (1-2): 52-4. [PMID:8084499]

4. Battaglia G, Busceti CL, Molinaro G, Biagioni F, Traficante A, Nicoletti F, Bruno V. (2006) Pharmacological activation of mGlu4 metabotropic glutamate receptors reduces nigrostriatal degeneration in mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. J Neurosci, 26: 7222-7229. [PMID:16822979]

5. Bennouar KE, Uberti MA, Melon C, Bacolod MD, Jimenez HN, Cajina M, Kerkerian-Le Goff L, Doller D, Gubellini P. (2013) Synergy between L-DOPA and a novel positive allosteric modulator of metabotropic glutamate receptor 4: implications for Parkinson's disease treatment and dyskinesia. Neuropharmacology, 66: 158-69. [PMID:22491024]

6. Beurrier C, Lopez S, Révy D, Selvam C, Goudet C, Lhérondel M, Gubellini P, Kerkerian-LeGoff L, Acher F, Pin JP et al.. (2009) Electrophysiological and behavioral evidence that modulation of metabotropic glutamate receptor 4 with a new agonist reverses experimental parkinsonism. FASEB J, 23 (10): 3619-28. [PMID:19525404]

7. Blednov YA, Walker D, Osterndorf-Kahanek E, Harris RA. (2004) Mice lacking metabotropic glutamate receptor 4 do not show the motor stimulatory effect of ethanol. Alcohol, 34 (2-3): 251-9. [PMID:15902920]

8. Brabet I, Parmentier ML, De Colle C, Bockaert J, Acher F, Pin JP. (1998) Comparative effect of L-CCG-I, DCG-IV and gamma-carboxy-L-glutamate on all cloned metabotropic glutamate receptor subtypes. Neuropharmacology, 37 (8): 1043-51. [PMID:9833633]

9. Bradley SR, Standaert DG, Rhodes KJ, Rees HD, Testa CM, Levey AI, Conn PJ. (1999) Immunohistochemical localization of subtype 4a metabotropic glutamate receptors in the rat and mouse basal ganglia. J Comp Neurol, 407 (1): 33-46. [PMID:10213186]

10. Charvin D, Conquet F. (2017) Brain-penetrant chromone oxime derivative for the therapy of levodopa-induced dyskinesia. Patent number: WO2017032874. Assignee: Prexton Therapeutics Sa. Priority date: 27/08/2015. Publication date: 02/03/2017.

11. Chaudhari N, Landin AM, Roper SD. (2000) A metabotropic glutamate receptor variant functions as a taste receptor. Nat Neurosci, 3 (2): 113-9. [PMID:10649565]

12. Chaudhari N, Yang H, Lamp C, Delay E, Cartford C, Than T, Roper S. (1996) The taste of monosodium glutamate: membrane receptors in taste buds. J Neurosci, 16 (12): 3817-26. [PMID:8656276]

13. Corti C, Aldegheri L, Somogyi P, Ferraguti F. (2002) Distribution and synaptic localisation of the metabotropic glutamate receptor 4 (mGluR4) in the rodent CNS. Neuroscience, 110 (3): 403-20. [PMID:11906782]

14. East SP, Bamford S, Dietz MG, Eickmeier C, Flegg A, Ferger B, Gemkow MJ, Heilker R, Hengerer B, Kotey A et al.. (2010) An orally bioavailable positive allosteric modulator of the mGlu4 receptor with efficacy in an animal model of motor dysfunction. Bioorg Med Chem Lett, 20 (16): 4901-5. [PMID:20638279]

15. Engers DW, Niswender CM, Weaver CD, Jadhav S, Menon UN, Zamorano R, Conn PJ, Lindsley CW, Hopkins CR. (2009) Synthesis and evaluation of a series of heterobiarylamides that are centrally penetrant metabotropic glutamate receptor 4 (mGluR4) positive allosteric modulators (PAMs). J Med Chem, 52 (14): 4115-8. [PMID:19469556]

16. Eriksen L, Thomsen C. (1995) [3H]-L-2-amino-4-phosphonobutyrate labels a metabotropic glutamate receptor, mGluR4a. Br J Pharmacol, 116 (8): 3279-87. [PMID:8719808]

17. Flor PJ, Lukic S, Rüegg D, Leonhardt T, Knöpfel T, Kuhn R. (1995) Molecular cloning, functional expression and pharmacological characterization of the human metabotropic glutamate receptor type 4. Neuropharmacology, 34 (2): 149-55. [PMID:7617140]

18. Frauli M, Hubert N, Schann S, Triballeau N, Bertrand HO, Acher F, Neuville P, Pin JP, Prézeau L. (2007) Amino-pyrrolidine tricarboxylic acids give new insight into group III metabotropic glutamate receptor activation mechanism. Mol Pharmacol, 71 (3): 704-12. [PMID:17167031]

19. Gasparini F, Bruno V, Battaglia G, Lukic S, Leonhardt T, Inderbitzin W, Laurie D, Sommer B, Varney MA, Hess SD, Johnson EC, Kuhn R, Urwyler S, Sauer D, Portet C, Schmutz M, Nicoletti F, Flor PJ. (1999) (R,S)-4-phosphonophenylglycine, a potent and selective group III metabotropic glutamate receptor agonist is anticonvulsive and neuroprotectivein vivo. J Pharmacol Exp Ther, 289: 1678-1687. [PMID:10336568]

20. Gasparini F, Inderbitzin W, Francotte E, Lecis G, Richert P, Dragic Z, Kuhn R, Flor PJ. (2000) (+)-4-phosphonophenylglycine (PPG) a new group III selective metabotropic glutamate receptor agonist. Bioorg Med Chem Lett, 10 (11): 1241-4. [PMID:10866390]

21. Gerlai R, Roder JC, Hampson DR. (1998) Altered spatial learning and memory in mice lacking the mGluR4 subtype of metabotropic glutamate receptor. Behav Neurosci, 112 (3): 525-32. [PMID:9676970]

22. Goudet C, Vilar B, Courtiol T, Deltheil T, Bessiron T, Brabet I, Oueslati N, Rigault D, Bertrand HO, McLean H et al.. (2012) A novel selective metabotropic glutamate receptor 4 agonist reveals new possibilities for developing subtype selective ligands with therapeutic potential. FASEB J, 26 (4): 1682-93. [PMID:22223752]

23. Han G, Hampson DR. (1999) Ligand binding to the amino-terminal domain of the mGluR4 subtype of metabotropic glutamate receptor. J Biol Chem, 274 (15): 10008-13. [PMID:10187777]

24. Hartveit E, Brandstätter JH, Enz R, Wässle H. (1995) Expression of the mRNA of seven metabotropic glutamate receptors (mGluR1 to 7) in the rat retina. An in situ hybridization study on tissue sections and isolated cells. Eur J Neurosci, 7 (7): 1472-83. [PMID:7551173]

25. Hayashi Y, Tanabe Y, Aramori I, Masu M, Shimamoto K, Ohfune Y, Nakanishi S. (1992) Agonist analysis of 2-(carboxycyclopropyl)glycine isomers for cloned metabotropic glutamate receptor subtypes expressed in Chinese hamster ovary cells. Br J Pharmacol, 107 (2): 539-43. [PMID:1330184]

26. Hong SP, Liu KG, Ma G, Sabio M, Uberti MA, Bacolod MD, Peterson J, Zou ZZ, Robichaud AJ, Doller D. (2011) Tricyclic thiazolopyrazole derivatives as metabotropic glutamate receptor 4 positive allosteric modulators. J Med Chem, 54 (14): 5070-81. [PMID:21688779]

27. Jimenez HN, Liu KG, Hong SP, Reitman MS, Uberti MA, Bacolod MD, Cajina M, Nattini M, Sabio M, Doller D. (2012) 4-(1-Phenyl-1H-pyrazol-4-yl)quinolines as novel, selective and brain penetrant metabotropic glutamate receptor 4 positive allosteric modulators. Bioorg Med Chem Lett, 22 (9): 3235-9. [PMID:22465637]

28. Jones CK, Bubser M, Thompson AD, Dickerson JW, Turle-Lorenzo N, Amalric M, Blobaum AL, Bridges TM, Morrison RD, Jadhav S et al.. (2012) The metabotropic glutamate receptor 4-positive allosteric modulator VU0364770 produces efficacy alone and in combination with L-DOPA or an adenosine 2A antagonist in preclinical rodent models of Parkinson's disease. J Pharmacol Exp Ther, 340 (2): 404-21. [PMID:22088953]

29. Jones CK, Engers DW, Thompson AD, Field JR, Blobaum AL, Lindsley SR, Zhou Y, Gogliotti RD, Jadhav S, Zamorano R et al.. (2011) Discovery, synthesis, and structure-activity relationship development of a series of N-4-(2,5-dioxopyrrolidin-1-yl)phenylpicolinamides (VU0400195, ML182): characterization of a novel positive allosteric modulator of the metabotropic glutamate receptor 4 (mGlu(4)) with oral efficacy in an antiparkinsonian animal model. J Med Chem, 54 (21): 7639-47. [PMID:21966889]

30. Kingston AE, Burnett JP, Mayne NG, Lodge D. (1995) Pharmacological analysis of 4-carboxyphenylglycine derivatives: comparison of effects on mGluR1 alpha and mGluR5a subtypes. Neuropharmacology, 34 (8): 887-94. [PMID:8532170]

31. Kogo N, Dalezios Y, Capogna M, Ferraguti F, Shigemoto R, Somogyi P. (2004) Depression of GABAergic input to identified hippocampal neurons by group III metabotropic glutamate receptors in the rat. Eur J Neurosci, 19 (10): 2727-40. [PMID:15147307]

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