Disease relevance of Grm2

• The metabotropic glutamate receptor 5 antagonist MPEP and the mGluR2 agonist LY379268 modify disease progression in a transgenic mouse model of Huntington's disease [1].
• Thus, behavioral deficits induced by mGluR2/3 blockade (such as delayed motor hyperactivity) are selectively reversed by clinically used antipsychotic drugs [2].

Psychiatry related information on Grm2

• Moreover, monocular deprivation remained effective in mice lacking mGluR2, and receptor expression levels were unchanged during the critical period in wild-type mice, indicating that experience-dependent plasticity is independent of LTD induction in visual cortex [3].
• Previous studies indicate that agonists of the group II metabotropic glutamate receptors (mGluRs), mGluR2 and mGluR3, may provide a novel approach for the treatment of anxiety disorders and schizophrenia [4].
• In the present study, male NMRI mice were injected with mGluR2/3 antagonist 2S-2-amino-2-(1S,2S-2-carboxycyclopropyl-1-yl)-3-(xanth-9-yl)propanoic acid (LY-341495) 30 min before being placed into novel arenas for automatic motor activity recording (2-h sessions) [2].
• The injection of AVP4-9 ameliorated PA task performance impairment induced by DCG-IV, an mGluR2/3 agonist [5].

High impact information on Grm2

• Subtype 2 of the metabotropic glutamate receptor (mGluR2) is expressed in the presynaptic elements of hippocampal mossy fiber-CA3 synapses [6].
• Impairment of hippocampal mossy fiber LTD in mice lacking mGluR2 [6].
• Knockout mice deficient in mGluR2 showed no histological changes and no alterations in basal synaptic transmission, paired-pulse facilitation, or tetanus-induced long-term potentiation (LTP) at the mossy fiber-CA3 synapses [6].
• They showed a significant increase in locomotor sensitization and conditioned place preference in association with repeated cocaine administration, indicating that mGluR2 contributes to behavioral responses implicated in reinforcement and addiction of cocaine [7].
• Here, we establish a fundamental role for type 2 metabotropic glutamate receptors (mGluR2) in long-term depression (LTD) of synaptic transmission within primary visual cortex [3].

Chemical compound and disease context of Grm2

• High doses of AVP4-9 exacerbated the PA task performance impairment induced by LY341495 (an mGluR2/3 antagonist), and PMA injection (1 mug) also exacerbated the impairment induced by the antagonist [5].

Biological context of Grm2

• Reverse transcription associated with polymerase chain reaction revealed that mGluR2 and mGluR3 mRNAs are present in striatal, cortical, and cerebellar neurons but not in striatal glial cells [8].
• MGS0039 attenuated both glutamate-induced inhibition of forskolin-evoked cyclic AMP formation in CHO cells expressing mGluR2 (IC50 = 20 nM) or mGluR3 (IC50 = 24 nM) and glutamate-increased [35S]GTPgammaS binding to mGluR2 (pA2 = 8.2), which means that MGS0039 acts as an antagonist [9].

Anatomical context of Grm2

• In the present study, the pharmacology of mGluRs negatively coupled to AC in several neuronal types and in glial cells was compared with the pharmacology of mGluR2, -3, and -4 [8].
• A small number of presynaptic axon terminals were labeled for mGluR2/3 immunoreactivity and formed asymmetrical synapses [10].
• The mechanical injury produced by the needle insertion in the cerebral cortex also produced enhanced expression of mGluR5 and mGluR2/3 in activated astrocytes proximal to the area of neuronal injury [11].
• Ca(L) channels were inhibited by the mGluR2/3 agonists. mGluR1/5 agonists accelerated and mGluR2/3 agonists suppressed the respiratory output, and correspondingly modified the hypoxic response of the respiratory center [12].
• The quantitative comparison of receptor distributions demonstrates that mGluR1 alpha and mGluR5, but not mGluR2, are highly compartmentalised in different plasma membrane domains [13].

Associations of Grm2 with chemical compounds

• This effect was mimicked by (2S,1'S,2'S)-2-(carboxycyclopropyl)glycine (L-CCG-I), a selective agonist of mGluR2/R3 receptors, but not by quisqualate at a concentration that stimulated inositol phosphate (InsP) synthesis, showing that mGluR1 and mGluR5 did not participate to this mechanism [14].
• (S)-4C3HPG was, however, an agonist at mGluR2 with an EC50 of 21 +/- 4 microM for inhibition of forskolin-stimulated cyclic AMP formation in BHK cells expressing the mGluR2 [15].
• Activation of mGluR2/3 reversibly depressed the fEPSP slopes in both the MPP and LPP, but no alterations were noted after PILO. mGluR8 activation selectively inhibited evoked responses in the LPP, but not in the MPP, and this level of inhibition did not change after PILO treatment [16].
• PCCG-IV was significantly more potent and selective as an antagonist at mGluR2 compared with previously described mGluR2 antagonists, including alpha-methyl-4-carboxyphenylglycine [17].
• 4. mGluR2/3 agonists (2S,1'R,2'R'3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV; 3 microM), (S)-4-carboxy-3-hydroxyphenylglycine (4C3HPG; 100-200 microM) and (S)-4-carboxyphenylglycine (4CPG; 300 microM) did not reduce NMDA current [18].

Physical interactions of Grm2

• In a previous work, we demonstrated that striatal neurons in primary culture expressed a mGluR that is negatively coupled to AC and that has a pharmacology different from that of mGluR2 [8].

Other interactions of Grm2

• These results suggest that mGluR2 or mGluR3 receptors suppress the activity of L-type Ca2+ channels by a mechanism involving Gi or G(o) proteins [14].
• Several cDNAs coding for metabotropic glutamate receptors (mGluR1-7) have now been isolated. mGluR1 and -5 are positively coupled to phospholipase C, whereas mGluR2, -3, -4, -6, and -7 are negatively coupled to adenylyl cyclase (AC) when they are expressed in Chinese hamster ovary or baby hamster kidney cells [8].
• Similar experiments revealed that cerebellar granule cells expressed mGluR2-like and mGluR4-like receptors [8].
• Recent work has shown that the activation of mGluR2, a metabotropic glutamate receptor, localized at granule cell dendrites suppresses the GABA inhibition of the mitral cells and permits the formation of a specific olfactory memory that faithfully reflects the memory formed at mating [19].
• By using immunofluorescence for metabotropic glutamate receptor 2 (mGluR2) and neurogranin as markers, we demonstrate the existence of five non-overlapping subsets of Golgi cells: about 65% are glycinergic/GABAergic and co-express both markers [20].

Analytical, diagnostic and therapeutic context of Grm2

• We were not able to detect message for mGluR2 in these cells using the reverse transcriptase-polymerase chain reaction [21].
• High resolution immunoelectron microscopy was used to study subcellular localization patterns of three metabotropic glutamate receptor subtypes (mGluR1alpha, mGluR5, and mGluR2/3) during postnatal development of mouse ventral posterior (VP) thalamic nucleus [10].
• Effects of mGluR1, mGluR2/3, and mGluR5 antagonists were then tested on parameters of ethanol self-administration behavior [22].
• Two small subsets (5-10%) also contain both neurotransmitters but express only mGluR2; they are distinguished by cell body size and location in the GCL [20].
• We examined the effect of (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV), a selective agonist of the mGluR 2/3 subtype, on excitotoxicity in mouse cortical cell cultures [23].

References