Disease relevance of GRIK4

• When we targeted the N-methyl-D-aspartic acid (NMDA) excitatory amino acid receptor with an AAV-delivered antisense oligonucleotide, however, the promoter determined whether focal seizure sensitivity was significantly attenuated or facilitated [1].
• These observations suggest that hyperalgesia and morphine tolerance may be interrelated at the level of the superficial laminae of the dorsal horn by common neural substrates that interact at the level of excitatory amino acid receptor activation and subsequent intracellular events [2].
• The immunohistochemical study with KA1 revealed that the surviving myocytes included in the infarcted region, especially in the ventricular aneurysm, expressed ir-ALC1 strongly in comparison with those in the noninfarcted or the control ventricles [3].
• Whole-cell recordings of amacrine and ganglion cells in the superfused retina-eyecup preparation of the mudpuppy were obtained in order to determine which excitatory amino acid receptor (EAAR) subtype mediates the synaptic responses of these neurons [4].
• Monoclonal antibody KA1 stained preferentially the basal-myoepithelial cells of the normal breast and FCD while staining tumor cell subpopulations in 4 of 31 carcinomas [5].

Psychiatry related information on GRIK4

• Cytogenetic and genetic evidence supports a role for the kainate-type glutamate receptor gene, GRIK4, in schizophrenia and bipolar disorder [6].
• The data suggest that no single excitatory amino acid receptor is selectively decreased in the caudate of Huntington's disease [7].
• Excitatory amino acid receptor-mediated excitotoxicity is postulated to play a role in the neurodegeneration in Alzheimer's disease [8].
• Anthropometric indices and life style practices of the indigenous Orang Asli adults in Lembah Belum, Grik of Peninsular Malaysia [9].

High impact information on GRIK4

• Here we present evidence that in mammalian central neurons tyrosine phosphorylation regulates the function of the NMDA (N-methyl-D-aspartate) receptor, a subtype of excitatory amino-acid receptor [10].
• Here we describe a new member of the rat excitatory amino-acid receptor gene family, KA-1, that has a 30% sequence similarity with the previously characterized alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunits GluR-A to -D [11].
• Increasing evidence suggests that afferent transmission from the receptor hair cells in the vestibular labyrinth to the vestibular nerve probably involves glutamate acting on a number of excitatory amino acid receptor subtypes [12].
• Ketamine, a phencyclidine hydrochloride derivative, is a dissociative anesthetic and a noncompetitive antagonist of the N-methyl-D-aspartate subtype of excitatory amino acid receptor [13].
• Until recently the metabotropic excitatory amino acid receptor could only be distinguished from ionotropic receptors by the nature of its second messenger system--phosphoinositide hydrolysis [14].

Chemical compound and disease context of GRIK4

• The carbazole degradative car-I gene cluster (carAaIBaIBbICIAcI) of Sphingomonas sp. strain KA1 is located on the 254-kb circular plasmid pCAR3 [15].
• The levels of the neuroprotective excitatory amino acid receptor antagonist kynurenic acid (KYNA) have been previously shown to be reduced in several regions of the brain of Huntington's disease (HD) patients [16].

Biological context of GRIK4

• GRIK4 and GRIK5 are located on separate chromosomes (Chrs) in all species [17].
• We also observed significant haplotype associations in seven SNP pairs in GRIK3 and in four SNP pairs in GRIK4 [18].
• We selected 16, 24 and 5 common single nucleotide polymorphisms (SNPs) distributed in the entire gene regions of GRIK3 (>240 kb), GRIK4 (>430 kb) and GRIK5 (>90 kb), respectively [18].
• Several candidate genes map to this region of the genome including a number of ion channel genes such as GRIK4, SCNB2, KCNJ5 and KCNJ1 [19].
• Two classes of binding site are resolved by their affinities (KA1 = 1.3 X 10(8) M; KA2 = 5.15 X 10(6) M) [20].

Anatomical context of GRIK4

• A neuron's combination of excitatory amino acid receptor subunits may regulate its response to excitatory inputs and further defines the role of identified subclasses of neurons in the complex circuitry of the cerebral cortex and may also indicate the basis for the apparent cellular selectivity of excitotoxic degenerative processes [21].
• The data indicate that the regional and cellular distribution of KA receptor subunit mRNAs in human hippocampus, neocortex and cerebellum largely parallels that in the corresponding areas of rat brain, albeit at lower levels, especially with regard to GluR5 and KA1 transcripts [22].
• KA1 mRNA was detected in the dentate gyrus but not reliably elsewhere [22].
• In the cerebral cortex, KA1-like immunostaining was observed in many pyramidal neuron somata, mainly in layer V, and along their apical dendrites [23].
• Here, we describe the presence of KA1-like immunoreactivity in both neurons and glial cells of the CNS, using a newly developed antiserum to a specific carboxy terminus epitope of the KA1 subunit [23].

Associations of GRIK4 with chemical compounds

• Here we report association studies of schizophrenia with polymorphisms in three kainate receptor genes: GRIK3, GRIK4 and GRIK5 [18].
• Ethanol inhibited to a similar extent KA-gated currents mediated by receptors composed of either GluR6 or GluR6 + KA1 subunits, and to a slightly lesser extent receptors composed of GluR6 + KA2 subunits [24].
• The mRNAs encoding kainic acid (KA) preferring glutamate receptor subunits (GluR5-7, KA1 and KA2) are differentially expressed in rat brain [22].
• In man propiverine is bound to serum albumin at a single site with high affinity (KA1 = 1.45 x 10(4) L mol-1) and at least two sites with low affinity (KA2 = 2.5 x 10(2) L mol-1) [25].
• Binding to the quisqualate-type excitatory amino acid receptor was unchanged in all regions except the stratum lacunosum moleculare CA1, where it was increased by 63% [26].

Physical interactions of GRIK4

• Metabotropic or "G-protein coupled" glutamate receptors (mGluRs) were discovered and established as a new type of excitatory amino acid receptor by their unique coupling mechanism (phosphoinositide hydrolysis) and pharmacological characteristics [27].

Regulatory relationships of GRIK4

• Metabotropic excitatory amino acid receptor activation stimulates phospholipase D in hippocampal slices [28].

Other interactions of GRIK4

• GRIK4 is the fifth gene shared by human Chr 11 and rat Chr 8, whereas GRIK5 is 1 out of the 12 genes that are located on both human Chr 19 and rat Chr 1 [17].
• HAP-1 cells express the AMPA/kainate receptor subunit genes GluRs 1, 3, and 4 and the kainate receptor subunit genes GluR6, KA1, and KA2 [29].
• Acute ethanol's effects were tested on GluR5 KA receptors that are expressed as homomers (GluR5-Q) or heteromers (GluR5-R + KA1 and GluR5-R + KA2) [24].
• The inhibition of NMDA receptors by ethanol leads to the depression of excitatory synaptic potentials mediated by this type of excitatory amino acid receptor [30].
• Microzonal decreases in the immunostaining for non-NMDA ionotropic excitatory amino acid receptor subunits GluR 2/3 and GluR 5/6/7 in the human epileptogenic neocortex [31].

Analytical, diagnostic and therapeutic context of GRIK4

• Reverse transcription-PCR (RT-PCR) and quantitative RT-PCR analyses revealed that two car gene clusters constituted operons, and their expression was induced when KA1 was exposed to carbazole, although the fdxI-fdrI and fdrII genes were expressed constitutively [15].
• We studied the effects of intrathecal LY293558, a competitive non-N-methyl-D-aspartate excitatory amino acid receptor antagonist, on motor and sensory function in rats to determine whether drugs blocking these receptors could potentially be used as alternative agents to local anesthetics for spinal anesthesia [32].
• In order to explore the relative contributions of the different ionotropic excitatory amino acid receptor subtypes to signalling in primary visual cortex, we have mapped their distributions in area 17 of adult ferret cerebral cortex by quantitative in vitro autoradiography [33].
• In this class of excitatory amino acid receptor antagonists NR2B antagonists have shown efficacy in neuroprotection, anti-hyperalgesic and anti-Parkinson animal models [34].
• In the mammalian cochlea, the analysis of excitatory amino acid receptor expression by the reverse transcription-polymease chain reaction (RT-PCR), in situ hybridization and immunochemistry has provided considerable evidence for glutamate as the afferent neurotransmitter [35].

References