Disease relevance of Grik1

• In addition, the regional, laminar, and morphological characteristics of GluR5/6/7-immunoreactive neurons bear a strong similarity to those of the neocortical neurons with heightened vulnerability in certain neurodegenerative disorders [1].
• 4. Kainate receptors in murine dorsal root ganglion neurons are likely to be composed of homomeric GluR5 subunits [2].
• Our results are consistent with the possibility that the effects of topiramate on clonic seizure activity are due to functional blockade of GluR5 kainate receptors [3].
• The metabotropic glutamate receptor 5 antagonist MPEP and the mGluR2 agonist LY379268 modify disease progression in a transgenic mouse model of Huntington's disease [4].
• Prostaglandin and protein kinase A-dependent modulation of vanilloid receptor function by metabotropic glutamate receptor 5: potential mechanism for thermal hyperalgesia [5].

High impact information on Grik1

• We find that LTP is reduced in mice lacking the GluR6, but not the GluR5, kainate receptor subunit [6].
• We report that disruption of the GluR5 subunit gene does not cause the loss of functional KARs in CA1 interneurons, nor does it prevent kainate-induced inhibition of evoked GABAergic synaptic transmission onto CA1 pyramidal cells [7].
• In addition, we show the presence of presynaptic KARs comprising the GluR6 but not the GluR5 subunit that modulate synaptic transmission between inhibitory interneurons [7].
• Kainate receptor activation affects GABAergic inhibition in the hippocampus by mechanisms that are thought to involve the GluR5 subunit [7].
• Mice lacking metabotropic glutamate receptor 5 show impaired learning and reduced CA1 long-term potentiation (LTP) but normal CA3 LTP [8].

Biological context of Grik1

• RNA editing of the codon that encodes the glutamine/arginine (Q/R) site in the second membrane domain (MD2) of glutamate receptor 5 (GluR5) and GluR6 kainate receptor subunits produces receptors with reduced calcium permeabilities and single-channel conductances [9].
• Alternative splicing is known to regulate surface expression of GluR5 and GluR6 subunits [10].
• Furthermore, the activation of GluR5 and GluR6 kainate receptor subtypes by endogenous glutamate during seizures may be associated with the drug-resistance phenomenon [11].
• 2. We found that homomeric GluR5 receptors can exhibit striking inter-cell variability in channel kinetics in response to the agonists kainate and glutamate [2].
• Pharmacology and toxicology of ATOA, an AMPA receptor antagonist and a partial agonist at GluR5 receptors [12].

Anatomical context of Grik1

• Additionally, synaptic potentiation was significantly reduced in the lateral amygdala of GluR6 but not GluR5 knock-out mice [13].
• Our findings reveal that KARs comprising GluR5 or GluR6 subunits can either suppress or facilitate glutamatergic excitatory transmission in the SG of acutely prepared adult mouse spinal cord slices [14].
• Modulation of excitatory synaptic transmission in the spinal substantia gelatinosa of mice deficient in the kainate receptor GluR5 and/or GluR6 subunit [14].
• GluR5 had a restricted distribution pattern, with high expression in the ventral pallidum, the islands of Calleja and pars compacta of the substantia nigra [15].
• Presynaptic modulation of inhibitory transmission between dorsal horn neurons was preserved in cells from either GluR5- or GluR6-deficient mice [16].

Associations of Grik1 with chemical compounds

• Distinct roles for the kainate receptor subunits GluR5 and GluR6 in kainate-induced hippocampal gamma oscillations [17].
• To address the role of glutamate receptor mRNA editing in the brain, we have made two strains of mice with mutations at amino acid 636, the Q/R-editing site in GluR5, using embryonic stem cell-mediated transgenesis [9].
• GluR5(RloxP/RloxP) mice encode an arginine at the Q/R site of the GluR5 subunit, whereas GluR5(wt(loxP)/wt(loxP)) mice encode a glutamine at this site, similar to wild-type mice [9].
• Here we show that responses to capsaicin or inflammatory pain were significantly reduced in mice lacking glutamate receptor 5 (GluR5) but not GluR6 subunits [13].
• In particular, the piperazine 6e represents a highly potent and selective antagonist to GluR5 [18].

Other interactions of Grik1

• In classic fear-memory tests, mice lacking GluR6 but not GluR5 showed a significant reduction in fear memory when measured 3, 7, or 14 d after training [13].
• The inhibition of glycogen synthase kinase 3beta by a metabotropic glutamate receptor 5 mediated pathway confers neuroprotection to Abeta peptides [19].
• In Western blot analysis, the temporal expression of GluR2/3 began to appear at 3 DIV, whereas GluR5/6/7 was already expressed in the undifferentiated cells [20].
• There was a tendency of GluR6/7 clusters to represent triad-associated contacts, whereas GluR5 clusters represented non-triad-associated contacts [21].
• We also performed double-labeling experiments with the ribbon-specific marker bassoon and with antibodies against GluR5 and GluR6/7 in order to define the position of the flat bipolar cell contacts with respect to the triads [21].

Analytical, diagnostic and therapeutic context of Grik1

• Pre- and postembedding immunocytochemistry and electron microscopy were used to localize GluR5 and GluR6/7 to specific synaptic contacts at the cone pedicle base [21].

References