Metabotropic glutamate receptor 8 explained

Metabotropic glutamate receptor 8 is a protein that in humans is encoded by the GRM8 gene.^{[1] [2]}

Function

L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. The metabotropic glutamate receptors are a family of G protein-coupled receptors, that have been divided into 3 groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes GRM1 and GRM5 and these receptors have been shown to activate phospholipase C. Group II includes GRM2 and GRM3 while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities. Alternative splice variants of GRM8 have been described but their full-length nature has not been determined.

Ligands

• (S)-3,4-DCPG: agonist^[3]
• AZ12216052: positive allosteric modulator^[4]

See also

• Metabotropic glutamate receptor

Further reading

• Scherer SW, Soder S, Duvoisin RM, Huizenga JJ, Tsui LC . The human metabotropic glutamate receptor 8 (GRM8) gene: a disproportionately large gene located at 7q31.3-q32.1 . Genomics . 44 . 2 . 232–236 . September 1997 . 9299241 . 10.1006/geno.1997.4842 . free .
• Wu S, Wright RA, Rockey PK, Burgett SG, Arnold JS, Rosteck PR, Johnson BG, Schoepp DD, Belagaje RM . 6 . Group III human metabotropic glutamate receptors 4, 7 and 8: molecular cloning, functional expression, and comparison of pharmacological properties in RGT cells . Brain Research. Molecular Brain Research . 53 . 1–2 . 88–97 . January 1998 . 9473604 . 10.1016/S0169-328X(97)00277-5 .
• Malherbe P, Kratzeisen C, Lundstrom K, Richards JG, Faull RL, Mutel V . Cloning and functional expression of alternative spliced variants of the human metabotropic glutamate receptor 8 . Brain Research. Molecular Brain Research . 67 . 2 . 201–210 . April 1999 . 10216218 . 10.1016/S0169-328X(99)00050-9 .
• Thomas NK, Wright RA, Howson PA, Kingston AE, Schoepp DD, Jane DE . (S)-3,4-DCPG, a potent and selective mGlu8a receptor agonist, activates metabotropic glutamate receptors on primary afferent terminals in the neonatal rat spinal cord . Neuropharmacology . 40 . 3 . 311–318 . March 2001 . 11166323 . 10.1016/S0028-3908(00)00169-6 . 2872874 .
• Enz R . The actin-binding protein Filamin-A interacts with the metabotropic glutamate receptor type 7 . FEBS Letters . 514 . 2–3 . 184–188 . March 2002 . 11943148 . 10.1016/S0014-5793(02)02361-X . 44474808 . free .
• Tang Z, El Far O, Betz H, Scheschonka A . Pias1 interaction and sumoylation of metabotropic glutamate receptor 8 . The Journal of Biological Chemistry . 280 . 46 . 38153–38159 . November 2005 . 16144832 . 10.1074/jbc.M508168200 . free .
• Kobayashi Y, Akiyoshi J, Kanehisa M, Ichioka S, Tanaka Y, Tsuru J, Hanada H, Kodama K, Isogawa K, Tsutsumi T . 6 . Lack of polymorphism in genes encoding mGluR 7, mGluR 8, GABA(A) receptor alfa-6 subunit and nociceptin/orphanin FQ receptor and panic disorder . Psychiatric Genetics . 17 . 1 . 9 . February 2007 . 17167337 . 10.1097/YPG.0b013e32801118bc .

Notes and References

1. Scherer SW, Duvoisin RM, Kuhn R, Heng HH, Belloni E, Tsui LC . Localization of two metabotropic glutamate receptor genes, GRM3 and GRM8, to human chromosome 7q . Genomics . 31 . 2 . 230–233 . January 1996 . 8824806 . 10.1006/geno.1996.0036 . free .
2. Web site: Entrez Gene: GRM8 glutamate receptor, metabotropic 8.
3. Thomas NK, Wright RA, Howson PA, Kingston AE, Schoepp DD, Jane DE . (S)-3,4-DCPG, a potent and selective mGlu8a receptor agonist, activates metabotropic glutamate receptors on primary afferent terminals in the neonatal rat spinal cord . Neuropharmacology . 40 . 3 . 311–318 . March 2001 . 11166323 . 10.1016/S0028-3908(00)00169-6 . 2872874 .
4. Duvoisin RM, Pfankuch T, Wilson JM, Grabell J, Chhajlani V, Brown DG, Johnson E, Raber J . 6 . Acute pharmacological modulation of mGluR8 reduces measures of anxiety . Behavioural Brain Research . 212 . 2 . 168–173 . October 2010 . 20385173 . 2892883 . 10.1016/j.bbr.2010.04.006 .