Metabotropic glutamate receptors model

Yao Y, Pattabiraman N, Michne WE, Huang X-P, Hampson DR. 2003. Molecular modeling and mutagenesis of the ligand binding pocket of the mGluR3 subtype of metabotropic glutamate receptor. J Neurochem 86 947-957. 

Fisher K, Lefebvre C, Coderre TJ (2002) Antinociceptive effects following intrathecal pretreatment with selective metabotropic glutamate receptor compounds in a rat model of neuropathic pain. Pharmacol Biochem Behav 73 411-418 Flajolet M, RakhUin S, Wang H, et al (2003) Protein phosphatase 2C binds selectively to and dephosphorylates metabotropic glutamate receptor 3. Proc Natl Acad Sci USA 100 16006-16011... 

Constantino, G., Macchiarulo, A., Pellicciari, R. Modeling of amino-terminal domains of group I metabotropic glutamate receptors structural motifs affecting ligand selectivity, J. Med. Chem. 1999, 42, 5390-5401. 

Zahn, P. K. and Brennan, T. J. Intrathecal metabotropic glutamate receptor antagonists do not decrease mechanical hyperalgesia in a rat model of postoperative pain, Anesth. Analg. 1998, 87, 1354-1359. 

In the third and last section, we will report the construction of a new pharmacophore model for metabotropic glutamate receptor subtype 4 (mGlu4R) agonists. In spite of the fact that the available dataset is particularly difficult for pharmacophore modeling, we will show that the validation methods used allowed us to have great confidence in the hypotheses generated. 

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... 

Mammalian y-aminobutyric addB receptors structure and function. Pharmacol Rev 54 247-64 Brakeman PR, Lanahan AA, O Brien R et al (1997) Homer a protein that selectively binds metabotropic glutamate receptors. Nature 386 284—8 Bremner JD, Krystal JH, Southwick SM, Chamey DS (1996) Noradrenergic mechanisms in stress and anxiety II. Preclinical studies. Synapse 23 28-38 Breysse N, Baunez C, Spooren W et al (2002) Chronic but not acute treatment with a metabotropic glutamate 5 receptor antagonist reverses the akinetic deficits in a rat model of parkinsonism. J Neurosd 22 5669-78... 

INVOLVEMENT OF ENDOCANNABINOID SIGNALING IN THE NEUROPROTECTIVE EFFECTS OF SUBTYPE 1 METABOTROPIC GLUTAMATE RECEPTOR ANTAGONISTS IN MODELS OF CEREBRAL... 

Goudet C, Chapuy E, AUoui A, Acher F, Pin JP, Eschalier A (2008) Group 111 metabotropic glutamate receptors inhibit hyperalgesia in animal models of inflammation and neuropathic pain. Pain 137 112-124... 

The very likely presence in the sweet taste receptor of cavities similar to those hosting Glu in mGluRl, a metabotropic glutamate receptor of known structure (Kunishima et al., 2000), tells us that the sweet taste of small molecular weight sweeteners can certainly be accounted for, even if the details will remain in part obscure, at least till a receptor structure with better resolution than homology models will be available. Can the taste of sweet proteins be also explained by the knowledge of the receptor There is no obvious answer. Let us first examine possible receptor models in detail. 

Kohara A, Takahashi M, Yatsugi S et al (2008) Neuroprotective effects of the selective type 1 metabotropic glutamate receptor antagonist YM-202074 in rat stroke models. Brain Res 1191 168-179... 

De Leonibus E, Manago F, Giordani F et al (2009) Metabotropic glutamate receptors 5 blockade reverses spatial memory deficits in a mouse model of Parkinson s disease. Neuropsychopharmacology 34 729-738... 

Mela F, Marti M, Dekundy A et al (2007) Antagonism of metabotropic glutamate receptor type 5 attenuates 1-DOPA-induced dyskinesia and its molecular and neurochemical correlates in a rat model of Parkinson s disease. J Neurochem 101 483 497... 

Monn JA, Valli MJ, Massey SM et al (1999) Synthesis, pharmacological characterization, and molecular modeling of heterobicyclic amino acids related to (+)-2-aminobicyclo[3.1.0] hexane-2, 6-dicarboxylic acid (LY354740) identification of two new potent, selective, and systemically active agonists for group II metabotropic glutamate receptors. J Med Chem 42 1027-1040... 

Govek SP, Bonnefous C, Hutchinson JH et al (2005) Benzazoles as allosteric potentiators of metabotropic glutamate receptor 2 (mGluR2) efficacy in an animal model for schizophrenia. Bioorg Med Chem Lett 15 4068-4072... 

Keywords Metabotropic glutamate receptors 3D-homology model Neuroprotective agents Amino terminal domain... 

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