MGluR, Metabotropic Glutamate Receptor

Eight metabotropic glutamate receptors (mGluRs) have been identified that embody three functional classes 282... 

However, overactivation of AMPA or KA receptors can also lead to intracellular Ca2+ overload and neurodegeneration. This maybe especially true under conditions where NMDA-receptor activity is reduced by extracellular acidity or a buildup of extracellular Zn2+ [ 12]. It is also true with respect to specific neuronal subpopulations that express AMPA-sensitive Ca2+ channels (see Ch. 15). G-protein-linked metabotropic glutamate receptors (mGluRs) appear not to mediate excitotoxicity directly but, rather, to modify the degree of excitotoxic injury. 

Macek, T. A., Schaffhauser, H., and Conn, P. J. (1998) Protein kinase C and A3 adenosine receptor activation inhibit presynaptic metabotropic glutamate receptor (mGluR) function and uncouple mGluRs from GTP-binding proteins. J. Neurosci. 18, 6138-6146. 

However, it is not the only mechanism, because drugs that do not work at NMDA receptors can impair memory (e.g., benzodiazepines). Other EAA receptors include the ionotropic AMPA and kainate receptors, and the metabotropic glutamate receptors (mGluR). 

Figure 8. GPCRs described using radar plots. From left to right metastatin receptor (GPR54), neuropeptide Y2 receptor and metabotropic glutamate receptor (mGluRS).

Bonsi R, Cuomo D., De Persis C., Centonze D., Bemardi G., Calabresi P., and Pisani A. (2005). Modulatory action of metabotropic glutamate receptor (mGluR) 5 on mGluRl function in striatal cholinergic interneurons. Neuiopharmacology 49(Suppl 1) 104—113. 

Good pharmacophore models are generally capable of predicting the bioactive conformation of the bound ligands. Jullian, Bessis and co-workers, for instance, have demonstrated that despite a more stable folded conformation in aqueous buffer, L-glutamate adopts an extended conformation when bound to metabotropic glutamate receptors (mGluR) [31, 32]. One year later, the publication of the... 

Heinbockel T, Heyward P, Conquet F, Ennis M. 2004. Regulation of main olfactory bulb mitral cell excitability by metabotropic glutamate receptor mGluR 1. J Neurophysiol 92 3085-3096. 

Romano C, Sesma L lA, McDonald CT, O Malley K, van den Pol AN, et al. 1995. Distribution of metabotropic glutamate receptor mGluRS immunoreactivity in rat brain. J Comp Neurol 355 455-469. 

---