Metabotropic glutamate receptor 4 is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
that in humans is encoded by the ''GRM4''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
.
Together with GRM6, GRM7 and GRM8 it belongs to
group III of the
metabotropic glutamate receptor
The metabotropic glutamate receptors, or mGluRs, are a type of glutamate receptor that are active through an indirect metabotropic process. They are members of the group C family of G-protein-coupled receptors, or GPCRs. Like all glutamate re ...
family. Group III receptors are linked to the inhibition of the cyclic AMP cascade.
Activation of GRM4 has potential therapeutic benefits in the treatment of
parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms beco ...
.
Splice variant "taste-GRM4" is involved in the perception of
umami
Umami ( from ja, 旨味 ), or savoriness, is one of the five basic tastes. It has been described as savory and is characteristic of broths and cooked meats.
People taste umami through taste receptors that typically respond to glutamates and ...
taste.
Ligands
Orthosteric
*
Cinnabarinic acid, a tryptophan metabolite
*LSP1-2111: agonist
* LSP4-2022: agonist
*
LSP2-9166
LSP2-9166 is a drug which acts as a selective agonist for the group III metabotropic glutamate receptors, with a reasonably potent EC50 of 70nM at mGluR4 and 220nM at mGluR7, and weaker activity of 1380nM at mGluR6 and 4800nM at mGluR8. It has ...
: mixed agonist at mGluR
4 and mGluR
7
Positive allosteric modulators (PAMs)
*
Foliglurax
Foliglurax (developmental code names PXT-002331, DT2331) is a positive allosteric modulator of the metabotropic glutamate receptor 4 (mGluR4), which is under development by Prexton Therapeutics for the treatment of Parkinson's disease. It reached ...
(PXT-002331, DT-1687)
* Tricyclic thiazolopyrazole derivative 22a: EC
50 = 9 nM, E
max = 120%
*
ML-128: EC
50 = 240 nM, E
max = 182%
* VU0652957 (AP-472) (Valiglurax)
* VU-0418506
* VU-001171: EC
50 = 650 nM, E
max = 141%, 36-fold shift
* VU-0155041: subtype-selective PAM, intrinsic allosteric agonist activity, robust in-vivo activity
*
PHCCC: PAM of mGluR4, negative allosteric modulator of
mGluR1,
direct agonist at
mGluR6
Glutamate receptor, metabotropic 6, also known as GRM6 or mGluR6, is a protein which in humans is encoded by the ''GRM6'' gene.
Function
L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ion ...
References
Further reading
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{{Metabotropic glutamate receptor modulators
Metabotropic glutamate receptors