Target type: molecularfunction
A G protein-coupled receptor that is activated by L-AP-4 and inhibits adenylate cyclase activity. [PMID:9016303]
Group III metabotropic glutamate receptors (mGluRs), specifically mGluR4, mGluR6, and mGluR8, are G protein-coupled receptors that play a crucial role in mediating the effects of glutamate, the primary excitatory neurotransmitter in the central nervous system. These receptors are primarily involved in presynaptic regulation of neurotransmitter release, contributing to the modulation of synaptic plasticity and neuronal excitability.
Upon glutamate binding, mGluR4, mGluR6, and mGluR8 activate a G protein signaling pathway, leading to the inhibition of adenylyl cyclase activity. This results in a decrease in intracellular cyclic adenosine monophosphate (cAMP) levels, which subsequently suppresses the activation of protein kinase A (PKA). This signaling cascade ultimately leads to the modulation of various downstream targets, including ion channels and other signaling proteins.
The molecular function of group III mGluRs is characterized by:
* **Presynaptic Inhibition of Neurotransmitter Release:** These receptors primarily function as presynaptic autoreceptors, inhibiting the release of glutamate and other neurotransmitters. This inhibitory effect is mediated by the reduction in cAMP levels and subsequent suppression of PKA activity, ultimately leading to the modulation of synaptic vesicle exocytosis.
* **Modulation of Neuronal Excitability:** Group III mGluRs contribute to the regulation of neuronal excitability by fine-tuning synaptic transmission. Their inhibitory effects on glutamate release and the downstream signaling pathways contribute to the maintenance of neuronal homeostasis and the control of neuronal firing patterns.
* **Role in Synaptic Plasticity:** The modulation of neurotransmitter release and neuronal excitability by group III mGluRs plays a significant role in synaptic plasticity, a fundamental process underlying learning and memory. The ability of these receptors to fine-tune synaptic strength and modify neuronal activity contributes to the dynamic nature of neural circuits.
* **Therapeutic Potential:** The involvement of group III mGluRs in various neurological and psychiatric disorders, including anxiety, depression, and epilepsy, highlights their potential as therapeutic targets. Modulation of their activity through pharmacological interventions offers promising avenues for the development of novel therapeutic strategies.
Overall, group III mGluRs act as presynaptic regulators of neurotransmitter release, playing a crucial role in modulating synaptic plasticity and neuronal excitability. Their intricate signaling pathways and diverse functions make them essential players in the complex workings of the central nervous system, offering potential avenues for therapeutic interventions.'
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| Protein | Definition | Taxonomy |
|---|---|---|
| Metabotropic glutamate receptor 8 | A metabotropic glutamate receptor 8 that is encoded in the genome of human. [PRO:DNx, UniProtKB:O00222] | Homo sapiens (human) |
| Metabotropic glutamate receptor 7 | A metabotropic glutamate receptor 7 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q14831] | Homo sapiens (human) |
| Compound | Definition | Classes | Roles |
|---|---|---|---|
| 2-amino-4-phosphonobutyric acid | 2-amino-4-phosphonobutyric acid: glutamate antagonist in locust muscle; structure; do not confuse with L-AP4, which is the propionic acid version | ||
| glutamic acid | glutamic acid : An alpha-amino acid that is glutaric acid bearing a single amino substituent at position 2. Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM. | glutamic acid; glutamine family amino acid; L-alpha-amino acid; proteinogenic amino acid | Escherichia coli metabolite; ferroptosis inducer; micronutrient; mouse metabolite; neurotransmitter; nutraceutical |
| quisqualic acid | Quisqualic Acid: An agonist at two subsets of excitatory amino acid receptors, ionotropic receptors that directly control membrane channels and metabotropic receptors that indirectly mediate calcium mobilization from intracellular stores. The compound is obtained from the seeds and fruit of Quisqualis chinensis. | non-proteinogenic alpha-amino acid | |
| plasmenylserine | O-phospho-L-serine : The L-enantiomer of O-phosphoserine. O-phosphoserine : A serine derivative that is serine substituted at the oxygen atom by a phosphono group. plasmenylserine: RN given refers to (L)-isomer | O-phosphoserine | EC 1.4.7.1 [glutamate synthase (ferredoxin)] inhibitor; EC 2.5.1.49 (O-acetylhomoserine aminocarboxypropyltransferase) inhibitor; EC 4.3.1.10 (serine-sulfate ammonia-lyase) inhibitor; Escherichia coli metabolite; human metabolite; mouse metabolite; Saccharomyces cerevisiae metabolite |
| 1-amino-1,3-dicarboxycyclopentane | 1-amino-1,3-dicarboxycyclopentane: RN given refers to (cis)-isomer | ||
| 2-amino-4-phosphonobutyric acid | (2S)-2-amino-4-phosphonobutanoic acid : A non-proteinogenc L-alpha-amino acid that is L-alpha-aminobutyric acid in which one of the hydrogens of the terminal methyl group has been replaced by a dihydroxy(oxido)-lambda(5)-phosphanyl group. It is a potent and selective agonist for the group III metabotropic glutamate receptors (mGluR4/6/7/8). | non-proteinogenic L-alpha-amino acid; phosphonic acids | metabotropic glutamate receptor agonist |
| eglumetad | eglumetad: LY-354740 is the active isomer, LY-366563 is the inactive isomer, and LY 314582 is the racemate; structure given in first source | L-alpha-amino acid | |
| 3,5-dihydroxyphenylglycine | (S)-3,5-dihydroxyphenylglycine : A glycine derivative that is L-alpha-phenylglycine substituted at positions 3 and 5 on the phenyl ring by hydroxy groups. | amino acid zwitterion; non-proteinogenic L-alpha-amino acid; resorcinols | |
| amn082 | N,N'-bis(diphenylmethyl)ethane-1,2-diamine : A diamine that is ethane-1,2-diamine in which both amino groups are substituted by diphenylmethyl groups. It is an allosteric agonist of the metabotropic glutamate receptor 7 (mGluR7). | benzenes; diamine; diarylmethane; secondary amino compound | metabotropic glutamate receptor agonist; neuroprotective agent |
| 6-methyl-2-(phenylethynyl)pyridine | 2-methyl-6-(phenylethynyl)pyridine : A methylpyridine that coinsists of 2-methylp[yridine bearing an additional phenylethynyl group at position 6. Potent and highly selective non-competitive antagonist at the mGlu5 receptor subtype (IC50 = 36 nM) and a positive allosteric modulator at mGlu4 receptors. Centrally active following systemic administration in vivo. Reverses mechanical hyperalgesia in the inflamed rat hind paw. 6-methyl-2-(phenylethynyl)pyridine: an mGlu5 antagonist | acetylenic compound; methylpyridines | anxiolytic drug; metabotropic glutamate receptor antagonist |
| sib 1757 | SIB 1757: a selective mGluR5 antagonist; structure in first source | ||
| l-2-(carboxypropyl)glycine | |||
| 2-(2,3-dicarboxycyclopropyl)glycine | |||
| 2r,4r-4-aminopyrrolidine-2,4-dicarboxylate | pyrrolidinedicarboxylic acid | ||
| sib 1893 | SIB 1893: a selective mGluR5 antagonist; structure in first source | ||
| 1-aminocyclopentane-1,3,4-tricarboxylic acid | 1-aminocyclopentane-1,3,4-tricarboxylic acid: metabolic glutamate receptor (mGluR) antagonist; structure in first source | ||
| ly 341495 | xanthenes | ||
| ly 404039 | LY404039 : An organic heterobicyclic compound that is (1S,5R)-2-thiabicyclo[3.1.0]hexane carrying oxo, oxo, amino, carboxy, and carboxy groups at positions 2, 2, 4S, 4S, and 6S, respectively. It is a potent agonist of group II metabotropic glutamate receptors mGluR2 mGluR3 (Ki = 149 nM and 92 nM, respectively) and exhibits antipsychotic and anxiolytic efficacy in animal models. | bridged compound; dicarboxylic acid; non-proteinogenic amino acid derivative; organic heterobicyclic compound; sulfone | antipsychotic agent; anxiolytic drug; dopamine agonist; metabotropic glutamate receptor agonist |
| mgs 0028 | MGS 0028: a group II mGluR agonist; structure in first source | ||
| ly 389795 | LY 389795: a group II metabotropic glutamate receptor agonist; structure in first source | ||
| ly 379268 | LY 379268 : An organic heterobicyclic compound that is (1R,5S)-2-oxabicyclo[3.1.0]hexane carrying amino, carboxy, and carboxy groups at positions 4R, 4R and 6R, respectively. It is a potent agonist of group II metabotropic glutamate receptors mGluR2 and mGluR3 (EC50 = 2.69 nM and 4.48 nM, respectively) that exhibits antipsychotic-like action in animal models of schizophrenia. LY 379268: group II metabotropic glutamate receptor agonist; structure in first source | amino dicarboxylic acid; bridged compound; organic heterobicyclic compound | antipsychotic agent; anxiolytic drug; metabotropic glutamate receptor agonist; neuroprotective agent |
| a 794282 | |||
| 3,4-dicarboxyphenylglycine | |||
| sp 203 | 3-fluoro-5-(2-(2-(fluoromethyl)thiazol-4-yl)ethynyl)benzonitrile: a radioligand for mGlu5 receptor; structure in first source | ||
| lsp4-2022 | LSP4-2022: structure in first source |