Disease relevance of Grm3

• Status epilepticus did not alter expression of mGluR1, mGluR3, or mGluR5 mRNAs [1].
• These observations show that during ultraviolet irradiation induced inflammation, the synthesis of mGluR3 messenger RNA is altered suggesting that regulation of metabotropic glutamate receptor expression may be instrumental in plastic changes within the spinal cord during the development of hyperalgesia and pain [2].
• Upregulation of metabotropic glutamate receptor subtype mGluR3 and mGluR5 in reactive astrocytes in a rat model of mesial temporal lobe epilepsy [3].

Psychiatry related information on Grm3

• 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].

High impact information on Grm3

• Immunohistochemical localization of metabotropic glutamate receptors, mGluR2 and mGluR3, in rat cerebellar cortex [5].
• Signal transduction, pharmacological properties, and expression patterns of two rat metabotropic glutamate receptors, mGluR3 and mGluR4 [6].
• Furthermore, the mGluR3 mRNA, unlike the other mRNAs for the metabotropic receptors, is highly expressed in glial cells throughout the brain regions.(ABSTRACT TRUNCATED AT 250 WORDS)[6]
• Blot and in situ hybridization analyses indicated that both mRNAs are widely distributed in the rat brain. mGluR3 mRNA is highly expressed in neuronal cells of the cerebral cortex and the caudate-putamen, and in granule cells of the hippocampal dentate gyrus [6].
• Neither the selective mGluR3 agonist, N-acetylaspartylglutamate (NAAG), nor the antagonist beta-NAAG, given intracerebrally, affected basal synaptic transmission. beta-NAAG significantly inhibited LTD expression [7].

Biological context of Grm3

• Bioinformatic analysis of these molecular targets showed that mGluR3 and cacna2d1 fall within chromosomal locations reported to be alcohol-related by the Collaborative Study on the Genetics of Alcoholism (COGA) as well as quantitative trait loci (QTL) studies [8].
• Comparison of the restricted mGluR2 and mGluR3 mRNA distributions with that of metabotropic ligand binding sites supports a possible presynaptic location for these receptors in the basal ganglia [9].
• We studied the signal transduction mechanism and pharmacological characteristics of the rat mGluR3 and mGluR4 subtypes in Chinese hamster ovary cells permanently expressing the cloned receptors [6].
• The metabotropic glutamate receptor mGluR3 is critically required for hippocampal long-term depression and modulates long-term potentiation in the dentate gyrus of freely moving rats [7].
• These data greatly expand knowledge of the range of second messenger cascades induced by mGluR3, and have implications for clinical conditions affected by NAAG and other group II mGluR agonists [10].

Anatomical context of Grm3

• Additionally, mGluR3 mRNA was found not only in neurones but also in putative glial cells [11].
• A further consistent feature in all species was labelling of astrocytes in the optic nerve/optic tract, superficial superior colliculus and brain at the collicular level with the antibody directed towards the Group II receptors, mGluR2 and mGluR3 [12].
• On immunoblot, the antibody reacted with both mGluR2 and mGluR3 in rat brain. mGluR2/3 immunoreactivity was expressed in cell bodies, dendrites, and axon terminals of Golgi cells, as well as in presumed glial processes [5].
• Using the kindling model of temporal lobe seizures, we evaluated the ability of local hippocampal injections of mGluR1 antisense or mGluR3 antisense oligonucleotides to suppress receptor expression and alter hippocampal kindling [13].
• These results show the important functional involvement of the limbic system together with the participation of components of different sensory systems in response to the activation of mGluR2 and mGluR3 with LY354740 and LY379268 [14].

Associations of Grm3 with chemical compounds

• In this model, inhibition of caspase activation is mediated through the group II metabotropic glutamate receptor, mGluR3 [15].
• Furthermore, we show that two mGluR3 agonists, the direct agonist (2R,4R)-4-aminopyrrolidine-2, 4-dicarboxylate (APDC) and N-acetyl-aspartyl-glutamate (NAAG) provide protection to neurons exposed to high glucose conditions, consistent with the concept that 2-PMPA neuroprotection is mediated by increased NAAG activity [15].
• Protection against glucose-induced neuronal death by NAAG and GCP II inhibition is regulated by mGluR3 [15].
• These data are consistent with the possibility that in primary cultures of cerebellar neurons, phosphoinositide responses may be predominantly mediated by mGluR1a, rather than mGluR5, and that cAMP inhibition involves preferentially mGluR4 and mGluR3 [16].
• The effect of 100 microM tACPD was reproduced by 100 microM quisqualate, an agonist of mGluR2 and mGluR3 subtypes [17].

Physical interactions of Grm3

• [(3)H]Quisqualic acid binding to mGluR1 required the presence of calcium (or magnesium) ions but not sodium or chloride ions while [(3)H]DCG-IV binding to mGluR3 was dependent upon both cations and anions [18].

Regulatory relationships of Grm3

• (1R,2S,5S,6S)-2-Amino-6-fluoro-4-oxobicyclo[3.1. 0]hexane-2,6-dicarboxylic acid monohydrate ((+)-14, MGS0028) exhibited a remarkably high degree of agonist activity for mGluR2 (K(i) = 0.570 +/- 0.10 nM) and mGluR3 (K(i) = 2.07 +/- 0.40 nM) expressed in CHO cells but not mGluR4, 6, 7, 1a, or 5 expressed in CHO cells (K(i) = >100 000 nM) [19].
• Both, group II mGluR-induced LTD and mGluR3-induced LTD were not abolished by mRNA/protein synthesis inhibition [20].
• Furthermore, mGluR3-induced LTD was not inhibited by NMDA receptor antagonists or altered by L-type voltage-gated calcium channel blockers [20].

Other interactions of Grm3

• Inhibition of GCP II or mGluR3 may represent a novel mechanism to treat neuronal degeneration under high-glucose conditions [15].
• Both mGluR3 and mGluR4 inhibit the forskolin-stimulated accumulation of intracellular cAMP formation in response to agonist interaction [6].
• In contrast, mGluR3 and mGluR5 were highly expressed at birth and decreased during maturation to adult levels of expression [21].
• Similar decreases of mGluR7 mRNA expression in the VB and Po were found at all time points, while mGluR3 mRNA expression was bilaterally increased in the reticular thalamic nucleus (Rt) [22].
• TGF-beta, a cytokine implicated in mGluR3-mediated neuroprotection, was also upregulated during the first 3 weeks after SE throughout the hippocampus [3].

Analytical, diagnostic and therapeutic context of Grm3

• Quantitative densitometry showed high mGluR3 and 5 messenger RNA levels especially in the superficial dorsal horn at birth, however these levels decreased with age [23].
• The examples we describe are that several different types of K(+) currents can be determined by patch clamp electrophysiology, of all the mGluRs only mGluR3 and 5 were detected by single cell RT-PCR, and that single cell Ca(2+) imaging shows that the mGluR5 receptor is functional [24].
• Furthermore, reverse transcription-PCR, Northern blotting, and immunohistochemistry analyses indicated expression of class II mGluR3 in pinealocytes [25].

References