Disease relevance of Grm8

• Moreover, mGluR8-/- mice are mildly insulin resistant, possibly as a result of being overweight [1].
• Increased measures of anxiety and weight gain in mice lacking the group III metabotropic glutamate receptor mGluR8 [1].
• Interaction between mGluR8 and calcium channels in photoreceptors is sensitive to pertussis toxin and occurs via G protein betagamma subunit signaling [2].

Psychiatry related information on Grm8

• Behavioral testing revealed a reduced locomotor activity of mGluR8-/- mice compared with wild-type mice during the first 3 days in a novel enclosed environment [1].

High impact information on Grm8

• Osteoclasts express mGluR8, a class III metabotropic glutamate receptor [3].
• Activation of mGluR8 by the group III mGluR agonists L-2-amino-4-phosphonobutyrate and L-serine-O-phosphate, or by glutamate itself, evokes a decrease in the intracellular calcium ion concentration ([Ca(2+)](i)) in isolated photoreceptors [4].
• Glutamate is the transmitter of photoreceptors, and thus mGluR8 functions as an autoreceptor [4].
• The down-regulation of the [Ca(2+)](i) in photoreceptors by mGluR8 provides evidence for an inhibitory feedback loop at the photoreceptor synapse in the mammalian retina [4].
• Similar to these receptors, stimulation by L-glutamate or L-2-amino-4-phosphonobutyrate (L-APB) of Chinese hamster ovary (CHO) cells stably transfected with mGluR8 result in the inhibition of forskolin-stimulated adenylyl cyclase [5].

Biological context of Grm8

• A novel metabotropic glutamate receptor, mGluR8, was identified by screening a mouse retina cDNA library [5].
• Performance deficits of mGluR8 knockout mice in learning tasks: the effects of null mutation and the background genotype [6].
• Whether the diverse phenotypic differences observed in mGluR8-/- mice result from the misregulation of a unique neural pathway, possibly in the thalamus or hypothalamus, or whether they are the consequence of multiple developmental and functional alterations in synaptic transmission, remains to be determined [1].
• Metabotropic glutamate receptors modulate neuronal activity but expression and alternative splicing of their subtypes (mGluR1-mGluR8) during early neuronal differentiation are essentially unknown [7].

Anatomical context of Grm8

• The pharmacology and expression of mGluR8 in mitral/tufted cells suggest it could be a presynaptic receptor modulating glutamate release by these cells at their axon terminals in the entorhinal cortex [5].
• In situ hybridization studies revealed a strong expression of the mGluR8 gene in the olfactory bulb, accessory olfactory bulb, and mammillary body [5].
• Here we analyze the consequences of a null mutation at the mGluR8 gene locus generated using homologous recombination in embryonic stem cells by comparing the learning performance of the mutants with that of wild type controls in the Morris water maze (MWM) and the context and cue dependent fear conditioning (CFC) [6].
• CONCLUSIONS: These results suggest that the function of mGluR8 of modulating the cytosolic Ca2+ concentration and thereby potentially the release of neurotransmitter from rod spherules, the axon terminal systems of rod photoreceptors, is mediated by a pertussis toxin-sensitive G protein potentially via the betagamma subunit [2].
• RESULTS: mGluR8 activation by the group III mGluR agonists l-2-amino-4-phosphonobutyrate and l-serine-O-phosphate or the physiological ligand l-glutamate produced a decrease in influx of extracellular Ca2+ into the cytosol [2].

Associations of Grm8 with chemical compounds

• 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 [8].

Other interactions of Grm8

• mGluR8 is a G-protein coupled metabotropic glutamate receptor expressed in the mammalian brain [6].
• Genetically manipulated mice (mGluR8 knockout and mGluR4/8 double knockout) and pharmacologically selective agonists were used to identify specific mGluR subtypes affected after PILO [8].

Analytical, diagnostic and therapeutic context of Grm8

• The role of mGluR8 as a presynaptic autoreceptor and its contribution to cognitive processes are hypothesized and the utility of gene targeting as compared to pharmacological methods is discussed [6].
• Here, we report by immunocytochemistry and physiology, to our knowledge, the first glutamate receptor to be found in terminals of photoreceptors in the mammalian retina-the group III metabotropic glutamate receptor mGluR8 [4].

References