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kainate receptor

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https://www.readbyqxmd.com/read/28100490/amino-terminal-domains-of-kainate-receptors-determine-the-differential-dependence-on-neto-auxiliary-subunits-for-trafficking
#1
Nengyin Sheng, Yun Stone Shi, Roger A Nicoll
The kainate receptor (KAR), a subtype of glutamate receptor, mediates excitatory synaptic responses at a subset of glutamatergic synapses. However, the molecular mechanisms underlying the trafficking of its different subunits are poorly understood. Here we use the CA1 hippocampal pyramidal cell, which lacks KAR-mediated synaptic currents, as a null background to determine the minimal requirements for the extrasynaptic and synaptic expression of the GluK2 subunit. We find that the GluK2 receptor itself, in contrast to GluK1, traffics to the neuronal surface and synapse efficiently and the auxiliary subunits Neto1 and Neto2 caused no further enhancement of these two trafficking processes...
January 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28073836/ionotropic-glutamate-receptors-activate-cell-signaling-in-response-to-glutamate-in-schwann-cells
#2
Wendy M Campana, Elisabetta Mantuano, Pardis Azmoon, Kenneth Henry, Michael A Banki, John H Kim, Donald P Pizzo, Steven L Gonias
In the peripheral nervous system, Schwann cells (SCs) demonstrate surveillance activity, detecting injury and undergoing trans-differentiation to support repair. SC receptors that detect peripheral nervous system injury remain incompletely understood. We used RT-PCR to profile ionotropic glutamate receptor expression in cultured SCs. We identified subunits required for assembly of N-methyl-d-aspartic acid (NMDA) receptors (NMDA-R), α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, and kainate receptors...
January 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28061403/berberine-ameliorates-intrahippocampal-kainate-induced-status-epilepticus-and-consequent-epileptogenic-process-in-the-rat-underlying-mechanisms
#3
Reza Sedaghat, Yosra Taab, Zahra Kiasalari, Siamak Afshin-Majd, Tourandokht Baluchnejadmojarad, Mehrdad Roghani
Status epilepticus (SE) is a life-threatening neurologic condition, instigating epileptogenesis to transform normal brain to an epileptic condition. SE is followed by spontaneous recurrent seizures (SRS) and final development of temporal lobe epilepsy (TLE) that is resistant to treatment. Neuroprotective strategies are increasingly put forward as a promising therapy to prevent and/or manage epileptic conditions. In this study, we investigated whether berberis alkaloid, i.e. berberine (BBR), could ameliorate intrahippocampal kainate-induced SE and its consequent epileptogenic process and to explore some underlying mechanisms...
January 3, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28041915/identification-of-multi-targeted-anti-migraine-potential-of-nystatin-and-development-of-its-brain-targeted-chitosan-nanoformulation
#4
Priti Girotra, Aman Thakur, Ajay Kumar, Shailendra Kumar Singh
The complex pathophysiology involved in migraine necessitates the drug treatment to act on several receptors simultaneously. The present investigation was an attempt to discover the unidentified anti-migraine activity of the already marketed drugs. Shared featured pharmacophore modeling was employed for this purpose on six target receptors (β2 adrenoceptor, Dopamine D3, 5HT1B, TRPV1, iGluR5 kainate and CGRP), resulting in the generation of five shared featured pharmacophores, which were further subjected to virtual screening of the ligands obtained from Drugbank database...
December 29, 2016: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28027456/immunohistochemical-localization-of-ionotropic-glutamate-receptors-in-the-rat-red-nucleus
#5
Zehra Minbay, Sema Serter Kocoglu, Duygu Gok Yurtseven, Ozhan Eyigor
In this study, we aimed to determine the presence as well as the diverse distribution of N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptor subunits in the rat red nucleus. Using adult Sprague-Dawley rats as the experimental animals, immunohistochemistry was performed on 30 µm thick coronal brain sections with antibodies against α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (GluA1-4), kainate (GluK1, GluK2/3, and GluK5), and NMDA (GluN1 and GluN2A) receptor subunits. The results showed that all ionotropic glutamate receptor subunits are expressed in the red nucleus...
December 21, 2016: Bosnian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28013091/effects-of-ly466195-a-selective-kainate-receptor-antagonist-on-ethanol-preference-and-drinking-in-rats
#6
Duncan Van Nest, Nicole S Hernandez, Henry R Kranzler, R Christopher Pierce, Heath D Schmidt
There is evidence that variation in the gene encoding a kainate receptor subunit contributes to alcohol dependence risk. Further, there is suggestive evidence that alcohol consumption is mediated, in part, by kainate receptors. In this study, we used a novel kainate receptor antagonist, LY466195, to examine the potential role of kainate receptors in alcohol drinking behavior using a rodent model of voluntary ethanol consumption. Male Sprague Dawley and Long Evans rats were given access to 20% ethanol using the intermittent two-bottle choice paradigm...
December 21, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27989680/prokineticin-system-modulation-as-a-new-target-to-counteract-the-amyloid-beta-toxicity-induced-by-glutamatergic-alterations-in-an-in%C3%A2-vitro-model-of-alzheimer-s-disease
#7
Silvia Caioli, Cinzia Severini, Teresa Ciotti, Fulvio Florenzano, Domenico Pimpinella, Pamela Petrocchi Passeri, Gianfranco Balboni, Patrizio Polisca, Roberta Lattanzi, Robert Nisticò, Lucia Negri, Cristina Zona
The accumulation of β-amyloid (Aβ) is one of the hallmarks of Alzheimer disease (AD). Beyond the inflammatory reactions promoted by Aβ, it has been demonstrated that the prokineticin (PK) system, composed of the chemokine prokineticin 2 (PK2) and its receptors, is involved in Aβ toxicity. In this study we have analyzed how the Aβ chronic treatment affects the glutamatergic transmission on neurons from primary cortical cultures, clearly demonstrating the PK system involvement on its action mechanism. In fact, we have observed a significant increase of the ionic current through the AMPA receptors in primary cortical neurons and an up-regulation of the PK system in cultures chronically treated with Aβ...
December 15, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27984177/hydrogen-sulfide-inhibits-giant-depolarizing-potentials-and-abolishes-epileptiform-activity-of-neonatal-rat-hippocampal-slices
#8
Aleksey V Yakovlev, Evgeniya D Kurmasheva, Rashid Giniatullin, Ilgam Khalilov, Guzel F Sitdikova
Hydrogen sulfide (H2S) is an endogenous gasotransmitter with neuroprotective properties that participates in the regulation of transmitter release and neuronal excitability in various brain structures. The role of H2S in the growth and maturation of neural networks however remains unclear. The aim of the present study is to reveal the effects of H2S on neuronal spontaneous activity relevant to neuronal maturation in hippocampal slices of neonatal rats. Sodium hydrosulfide (NaHS) (100 μM), a classical donor of H2S produced a biphasic effect with initial activation and subsequent concentration-dependent suppression of network-driven giant depolarizing potentials (GDPs) and neuronal spiking activity...
October 27, 2016: Neuroscience
https://www.readbyqxmd.com/read/27889096/novel-functional-properties-of-drosophila-cns-glutamate-receptors
#9
Yan Li, Poorva Dharkar, Tae-Hee Han, Mihaela Serpe, Chi-Hon Lee, Mark L Mayer
Phylogenetic analysis reveals AMPA, kainate, and NMDA receptor families in insect genomes, suggesting conserved functional properties corresponding to their vertebrate counterparts. However, heterologous expression of the Drosophila kainate receptor DKaiR1D and the AMPA receptor DGluR1A revealed novel ligand selectivity at odds with the classification used for vertebrate glutamate receptor ion channels (iGluRs). DKaiR1D forms a rapidly activating and desensitizing receptor that is inhibited by both NMDA and the NMDA receptor antagonist AP5; crystallization of the KaiR1D ligand-binding domain reveals that these ligands stabilize open cleft conformations, explaining their action as antagonists...
December 7, 2016: Neuron
https://www.readbyqxmd.com/read/27847705/a-model-of-glial-scarring-analogous-to-the-environment-of-a-traumatically-injured-spinal-cord-using-kainate
#10
Jong Yoon Yoo, Chang Ho Hwang, Hea Nam Hong
OBJECTIVE: To develop an in vitro model analogous to the environment of traumatic spinal cord injury (SCI), the authors evaluated change of astrogliosis following treatments with kainate and/or scratch, and degree of neurite outgrowth after treatment with a kainate inhibitor. METHODS: Astrocytes were obtained from the rat spinal cord. Then, 99% of the cells were confirmed to be GFAP-positive astrocytes. For chemical injury, the cells were treated with kainate at different concentrations (10, 50 or 100 µM)...
October 2016: Annals of Rehabilitation Medicine
https://www.readbyqxmd.com/read/27845167/synapse-organization-and-modulation-via-c1q-family-proteins-and-their-receptors-in-the-central-nervous-system
#11
REVIEW
Keiko Matsuda
Several C1q family members, related to the C1q complement component are extensively expressed in the central nervous system. Cbln1, which belongs to the Cbln subfamily of C1q proteins and released from cerebellar granule cells, plays an indispensable role in the synapse formation and function at parallel fiber-Purkinje cell synapses. This is achieved by formation of a trans-synaptic tripartite complex which is composed of one unit of the Cbln1 hexamer, monomeric neurexin (NRX) containing a splice site 4 insertion at presynaptic terminals and the postsynaptic GluD2 dimers...
November 12, 2016: Neuroscience Research
https://www.readbyqxmd.com/read/27791085/molecular-lock-regulates-binding-of-glycine-to-a-primitive-nmda-receptor
#12
Alvin Yu, Robert Alberstein, Alecia Thomas, Austin Zimmet, Richard Grey, Mark L Mayer, Albert Y Lau
The earliest metazoan ancestors of humans include the ctenophore Mnemiopsis leidyi The genome of this comb jelly encodes homologs of vertebrate ionotropic glutamate receptors (iGluRs) that are distantly related to glycine-activated NMDA receptors and that bind glycine with unusually high affinity. Using ligand-binding domain (LBD) mutants for electrophysiological analysis, we demonstrate that perturbing a ctenophore-specific interdomain Arg-Glu salt bridge that is notably absent from vertebrate AMPA, kainate, and NMDA iGluRs greatly increases the rate of recovery from desensitization, while biochemical analysis reveals a large decrease in affinity for glycine...
November 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27766534/the-good-and-the-bad-of-glutamate-receptor-rna-editing
#13
Alice Filippini, Daniela Bonini, Luca La Via, Alessandro Barbon
Glutamate receptors play a key role in excitatory synaptic transmission and plasticity in the central nervous system (CNS). Their channel properties are largely dictated by the subunit composition of tetrameric receptors. Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate channels are assembled from GluA1-4 AMPA or GluK1-5 kainate receptor subunits. However, their functional properties are highly modulated by a post-transcriptional mechanism called RNA editing. This process involves the enzymatic deamination of specific adenosines (A) into inosines (I) in pre-messenger RNA...
October 20, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27765511/design-synthesis-and-structure-activity-relationships-of-novel-phenylalanine-based-amino-acids-as-kainate-receptors-ligands
#14
Ewa Szymańska, Paulina Chałupnik, Katarzyna Szczepańska, Ana Maria Cuñado Moral, Darryl S Pickering, Birgitte Nielsen, Tommy N Johansen, Katarzyna Kieć-Kononowicz
A new series of carboxyaryl-substituted phenylalanines was designed, synthesized and pharmacologically characterized in vitro at native rat ionotropic glutamate receptors as well as at cloned homomeric kainate receptors GluK1-GluK3. Among them, six compounds bound to GluK1 receptor subtypes with reasonable affinity (Ki values in the range of 4.9-7.5μM). A structure-activity relationship (SAR) for the obtained series, focused mainly on the pharmacological effect of structural modifications in the 4- and 5-position of the phenylalanine ring, was established...
November 15, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27755061/lassbio-1422-a-new-molecular-scaffold-with-efficacy-in-animal-models-of-schizophrenia-and-disorders-of-attention-and-cognition
#15
Andresa H Betti, Camila B Antonio, Thais E T Pompeu, Thaise S Martins, Vivian Herzfeldt, Eveline D Stolz, Carlos A M Fraga, Eliezer Barreiro, François Noël, Stela M K Rates
Aiming to identify new antipsychotic lead-compounds, our group has been working on the design and synthesis of new N-phenylpiperazine derivatives. Here, we characterized LASSBio-1422 as a pharmacological prototype of this chemical series. Adult male Wistar rats and CF1 mice were used for in-vitro and in-vivo assays, respectively. LASSBio-1422 [1 and 5 mg/kg, postoperatively (p.o.)] inhibited apomorphine-induced climbing as well as ketamine-induced hyperlocomotion (1 and 5 mg/kg, p.o.), animal models predictive of efficacy on positive symptoms...
October 13, 2016: Behavioural Pharmacology
https://www.readbyqxmd.com/read/27733539/epigenetic-regulation-of-glutamic-acid-decarboxylase-67-in-a-hippocampal-circuit
#16
Sivan Subburaju, Andrew J Coleman, Miles G Cunningham, W Brad Ruzicka, Francine M Benes
GABAergic dysfunction in hippocampus, a key feature of schizophrenia (SZ), may contribute to cognitive impairment in this disorder. In stratum oriens (SO) of sector CA3/2 of the human hippocampus, a network of genes involved in the regulation of glutamic acid decarboxylase GAD67 has been identified. Several of the genes in this network including epigenetic factors histone deacetylase 1 (HDAC1) and death-associated protein 6 (DAXX), the GABAergic enzyme GAD65 as well as the kainate receptor (KAR) subunits GluR6 and 7 show significant changes in expression in this area in SZ...
October 12, 2016: Cerebral Cortex
https://www.readbyqxmd.com/read/27717879/unravelling-cortico-hypothalamic-pathways-regulating-unconditioned-fear-induced-antinociception-and-defensive-behaviours
#17
Luiz Luciano Falconi-Sobrinho, Tayllon Dos Anjos-Garcia, Daoud Hibrahim Elias-Filho, Norberto Cysne Coimbra
The medial prefrontal cortex can influence unconditioned fear-induced defensive mechanisms organised by diencephalic neurons that are under tonic GABAergic inhibition. The posterior hypothalamus (PH) is involved with anxiety- and panic attack-like responses. To understand this cortical mediation, our study characterised anterior cingulate cortex (ACC)-PH pathways and investigated the effect of ACC local inactivation with lidocaine. We also investigated the involvement of PH ionotropic glutamate receptors in the defensive behaviours and fear-induced antinociception by microinjecting NBQX (an AMPA/kainate receptor antagonist) and LY235959 (a NMDA receptor antagonist) into the PH...
February 2017: Neuropharmacology
https://www.readbyqxmd.com/read/27669960/molecular-determinants-for-the-strictly-compartmentalized-expression-of-kainate-receptors-in-ca3-pyramidal-cells
#18
Sabine Fièvre, Mario Carta, Ingrid Chamma, Virginie Labrousse, Olivier Thoumine, Christophe Mulle
Distinct subtypes of ionotropic glutamate receptors can segregate to specific synaptic inputs in a given neuron. Using functional mapping by focal glutamate uncaging in CA3 pyramidal cells (PCs), we observe that kainate receptors (KARs) are strictly confined to the postsynaptic elements of mossy fibre (mf) synapses and excluded from other glutamatergic inputs and from extrasynaptic compartments. By molecular replacement in organotypic slices from GluK2 knockout mice, we show that the faithful rescue of KAR segregation at mf-CA3 synapses critically depends on the amount of GluK2a cDNA transfected and on a sequence in the GluK2a C-terminal domain responsible for interaction with N-cadherin...
2016: Nature Communications
https://www.readbyqxmd.com/read/27663701/structure-and-symmetry-inform-gating-principles-of-ionotropic-glutamate-receptors
#19
REVIEW
Shujia Zhu, Eric Gouaux
Ionotropic glutamate receptors (iGluRs) transduce signals derived from release of the excitatory neurotransmitter glutamate from pre-synaptic neurons into excitation of post-synaptic neurons on a millisecond time-scale. In recent years, the elucidation of full-length iGluR structures of NMDA, AMPA and kainate receptors by X-ray crystallography and single particle cryo-electron microscopy has greatly enhanced our understanding of the interrelationships between receptor architecture and gating mechanism. Here we briefly review full-length iGluR structures and discuss the similarities and differences between NMDA receptors and non-NMDA iGluRs...
January 2017: Neuropharmacology
https://www.readbyqxmd.com/read/27663136/inhibition-of-calcium-permeable-and-calcium-impermeable-ampa-receptors-by-perampanel-in-rat-brain-neurons
#20
Oleg I Barygin
Perampanel is an antiepileptic drug that is used to treat partial-onset seizures and generalized tonic-clonic seizures. It is a highly selective AMPA receptor allosteric antagonist. However, published data on perampanel activity vary in different studies. In the present work we studied the inhibition of native calcium-permeable and calcium-impermeable AMPA receptors in rat brain neurons by perampanel using whole-cell patch clamp technique. We found that inhibitory activity and kinetics of perampanel action do not differ between calcium-permeable AMPA receptors of rat giant striatum interneurons and calcium-impermeable receptors of hippocampal CA1 pyramidal neurons (the IC50 value about 60nM)...
October 28, 2016: Neuroscience Letters
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