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Glycine receptor

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https://www.readbyqxmd.com/read/28202787/dysregulated-glycine-signaling-contributes-to-increased-impulsivity-during-protracted-alcohol-abstinence
#1
Cristina Irimia, Matthew W Buczynski, Luis A Natividad, Sarah A Laredo, Nathaniel Avalos, Loren H Parsons
Persons with alcoholism who are abstinent exhibit persistent impairments in the capacity for response inhibition, and this form of impulsivity is significantly associated with heightened relapse risk. Brain-imaging studies implicate aberrant prefrontal cortical function in this behavioral pathology, although the underlying mechanisms are not understood. Here we present evidence that deficient activation of glycine and serine release in the ventral medial prefrontal cortex (vmPFC) contributes to increased motor impulsivity during protracted abstinence from long-term alcohol exposure...
February 15, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28202572/differential-regulation-of-nmda-receptors-by-d-serine-and-glycine-in-mammalian-spinal-locomotor-networks
#2
David Acton, Gareth Brian Miles
Activation of N-methyl-D-aspartate receptors (NMDARs) requires the binding of a co-agonist, either D-serine or glycine, in addition to glutamate. Changes in occupancy of the co-agonist binding site are proposed to modulate neural networks including those controlling swimming in frog tadpoles. Here, we characterize regulation of the NMDAR co-agonist binding site in mammalian spinal locomotor networks. Blockade of NMDARs by D(-)-2-amino-5-phosphonopentanoic acid (D-APV) or 5,7-dichlorokynurenic acid reduced the frequency and amplitude of pharmacologically induced locomotor-related activity recorded from the ventral roots of spinal-cord preparations from neonatal mice...
February 15, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28197549/activation-dependent-rapid-postsynaptic-clustering-of-glycine-receptors-in-mature-spinal-cord-neurons
#3
Yoshihisa Nakahata, Kei Eto, Hideji Murakoshi, Miho Watanabe, Toshihiko Kuriu, Hiromi Hirata, Andrew J Moorhouse, Hitoshi Ishibashi, Junichi Nabekura
Inhibitory synapses are established during development but continue to be generated and modulated in strength in the mature nervous system. In the spinal cord and brainstem, presynaptically released inhibitory neurotransmitter dominantly switches from GABA to glycine during normal development in vivo. While presynaptic mechanisms of the shift of inhibitory neurotransmission are well investigated, the contribution of postsynaptic neurotransmitter receptors to this shift is not fully elucidated. Synaptic clustering of glycine receptors (GlyRs) is regulated by activation-dependent depolarization in early development...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28192731/isotrifoliol-inhibits-pro-inflammatory-mediators-by-suppression-of-tlr-nf-%C3%AE%C2%BAb-and-tlr-mapk-signaling-in-lps-induced-raw264-7-cells
#4
Hua Li, Jeong-Hyun Yoon, Hyo-Jun Won, Hyeon-Seon Ji, Heong Joo Yuk, Ki Hun Park, Ho-Yong Park, Tae-Sook Jeong
Soybeans, produced by Glycine max (L.) Merr., contain high levels of isoflavones, such as genistein and daidzein. However, soy leaves contain more diverse and abundant flavonol glycosides and coumestans, as compared to the soybean. This study investigated the anti-inflammatory effects of the major coumestans present in soy leaf (coumestrol, isotrifoliol, and phaseol) in lipopolysaccharide (LPS)-induced RAW264.7 cells. Coumestans significantly reduced LPS-induced nitric oxide (NO), prostaglandin E2 (PGE2), and reactive oxygen species (ROS) production; isotrifoliol had the most potent anti-inflammatory activity...
February 10, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28186717/gating-motions-and-stationary-gating-properties-of-ionotropic-glutamate-receptors-computation-meets-electrophysiology
#5
Huan-Xiang Zhou
Ionotropic glutamate receptors (iGluRs) are tetrameric ligand-gated ion channels essential to all aspects of brain function, including higher order processes such as learning and memory. For decades, electrophysiology was the primary means for characterizing the function of iGluRs and gaining mechanistic insight. Since the turn of the century, structures of isolated water-soluble domains and transmembrane-domain-containing constructs have provided the basis for formulating mechanistic hypotheses. Because these structures only represent sparse, often incomplete snapshots during iGluR activation, significant gaps in knowledge remain regarding structures, energetics, and dynamics of key substates along the functional processes...
February 10, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28181832/a-tumor-targeting-crgd-egfr-sirna-conjugate-and-its-anti-tumor-effect-on-glioblastoma-in-vitro-and-in-vivo
#6
Shuai He, Bohong Cen, Lumin Liao, Zhen Wang, Yixin Qin, Zhuomin Wu, Wenjie Liao, Zhongyi Zhang, Aimin Ji
The epidermal growth factor receptor (EGFR) is an important anti-tumor target. The development of novel molecular-targeted anti-tumor drugs that can target the interior of tumor cells and specifically silence EGFR expression is valuable and promising. In this work, a promising anti-tumor conjugate comprising methoxy-modified EGFR siRNA and cyclic arginine-glycine-aspartic acid (cRGD) peptides, which selectively bind to αvβ3 integrins, was synthesized and examined. To prepare cRGD-EGFR siRNA (cRGD-siEGFR), cRGD was covalently conjugated to the 5'-end of an siRNA sense strand using a thiol-maleimide linker...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28174298/the-startle-disease-mutation-e103k-impairs-activation-of-human-homomeric-%C3%AE-1-glycine-receptors-by-disrupting-an-intersubunit-salt-bridge-across-the-agonist-binding-site
#7
Fatemah Safar, Elliot Hurdiss, Marios Erotocritou, Timo Greiner, Remigijus Lape, Mark W Irvine, Guangyu Fang, David Jane, Rilei Yu, Marc A Dämgen, Philip C Biggin, Lucia G Sivilotti
Glycine receptors (GlyR) belong to the pentameric ligand gated ion channel (pLGIC) superfamily and mediate fast inhibitory transmission in the vertebrate CNS. Disruption of glycinergic transmission by inherited mutations produces startle disease in man. Many startle mutations are in GlyRs and provide useful clues to the function of the channel domains. E103K is one of few startle mutations found in the extracellular agonist binding site of the channel, in loop A of the principal side of the subunit interface...
February 7, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28167900/parvalbumin-neurons-of-the-ventrolateral-hypothalamic-parvafox-nucleus-receive-a-glycinergic-input-a-gene-microarray-study
#8
Viktoria Szabolcsi, Gioele W Albisetti, Marco R Celio
The ventrolateral hypothalamic parvafox (formerly called PV1-Foxb1) nucleus is an anatomical entity of recent discovery and unknown function. With a view to gaining an insight into its putative functional role(s), we conducted a gene-microarray analysis and, armed with the forthcoming data, controlled the results with the Allen databases and the murine BrainStars (B(*)) database. The parvafox nucleus was specifically sampled by laser-capture microdissection and the transcriptome was subjected to a microarray analysis on Affymetrix chips...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28161374/chronic-gabaergic-blockade-in-the-spinal-cord-in%C3%A2-vivo-induces-motor-alterations-and-neurodegeneration
#9
Uri Nimrod Ramírez-Jarquín, Ricardo Tapia
Inhibitory GABAergic and glycinergic neurotransmission in the spinal cord play a central role in the regulation of neuronal excitability, by maintaining a balance with the glutamate-mediated excitatory transmission. Glutamatergic agonists infusion in the spinal cord induce motor neuron death by excitotoxicity, leading to motor deficits and paralysis, but little is known on the effect of the blockade of inhibitory transmission. In this work we studied the effects of GABAergic and glycinergic blockade, by means of microdialysis perfusion (acute administration) and osmotic minipumps infusion (chronic administration) of GABA and glycine receptors antagonists directly in the lumbar spinal cord...
February 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28143398/a-noninvasive-optical-approach-for-assessing-chloride-extrusion-activity-of-the-k-cl-cotransporter-kcc2-in-neuronal-cells
#10
Anastasia Ludwig, Claudio Rivera, Pavel Uvarov
BACKGROUND: Cation-chloride cotransporters (CCCs) are indispensable for maintaining chloride homeostasis in multiple cell types, but K-Cl cotransporter KCC2 is the only CCC member with an exclusively neuronal expression in mammals. KCC2 is critical for rendering fast hyperpolarizing responses of ionotropic γ-aminobutyric acid and glycine receptors in adult neurons, for neuronal migration in the developing central nervous system, and for the formation and maintenance of small dendritic protrusions-dendritic spines...
January 31, 2017: BMC Neuroscience
https://www.readbyqxmd.com/read/28132911/effect-of-alpha-lipoic-acid-on-leukotriene-a4-hydrolase
#11
María José Torres, Angélica Fierro, C David Pessoa-Mahana, Javier Romero-Parra, Gonzalo Cabrera, Mario Faúndez
Leukotriene A4 hydrolase is a soluble enzyme with epoxide hydrolase and aminopeptidase activities catalysing the conversion of leukotriene A4 to leukotriene B4 and the hydrolysis of the peptide proline-glycine-proline. Imbalances in leukotriene B4 synthesis are related to several pathologic conditions. Currently there are no available drugs capable to modulate the synthesis of leukotriene B4 or to block its receptors. Here we show the inhibitory profile of alpha lipoic acid on the activity of leukotriene A4 Hydrolase...
January 26, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28132660/grin3b-missense-mutation-as-an-inherited-risk-factor-for-schizophrenia-whole-exome-sequencing-in-a-family-with-a-familiar-history-of-psychotic-disorders
#12
Tobias Hornig, Björn Grüning, Kousik Kundu, Torsten Houwaart, Rolf Backofen, Knut Biber, Claus Normann
Glutamate is the most important excitatory neurotransmitter in the brain. The N-methyl-D-aspartate (NMDA) receptor is a glutamate-gated ionotropic cation channel that is composed of several subunits and modulated by a glycine binding site. Many forms of synaptic plasticity depend on the influx of calcium ions through NMDA receptors, and NMDA receptor dysfunction has been linked to a number of neuropsychiatric disorders, including schizophrenia. Whole-exome sequencing was performed in a family with a strong history of psychotic disorders over three generations...
30, 2017: Genetics Research
https://www.readbyqxmd.com/read/28130358/inhibition-mediated-by-glycinergic-and-gabaergic-receptors-on-excitatory-neurons-in-mouse-superficial-dorsal-horn-is-location-specific-but-modified-by-inflammation
#13
Tomonori Takazawa, Papiya Choudhury, Chi-Kun Tong, Charles M Conway, Grégory Scherrer, Pamela D Flood, Jun Mukai, Amy B MacDermott
: The superficial dorsal horn is the synaptic termination site for many peripheral sensory fibers of the somatosensory system. A wide range of sensory modalities are represented by these fibers including pain, itch and temperature. Because local inhibition in the dorsal horn, specifically that mediated by the inhibitory amino acids GABA and glycine, is importantly involved in signal processing there, we investigated regional inhibitory control of excitatory interneurons under control conditions and peripheral inflammation-induced mechanical allodynia...
January 27, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28125320/start-me-up-revision-of-evidences-that-atgrp3-acts-as-a-potential-switch-for-atwak1
#14
Amanda Mangeon, Adriana Dias Menezes-Salgueiro, Gilberto Sachetto-Martins
AtGRP3 is a glycine-rich protein from Arabidopsis thaliana shown to interact with the extracellular domain of the receptor-like kinase (RLK) AtWAK1. Based on previous functional data for AtWAK1, a model was proposed that AtGRP3 when bound to this RLK would negatively regulate its kinase activity, inhibiting cell expansion. Here, we review recent functional studies on AtGRP3 that corroborate this model and suggest that AtGRP3/AtWAK1 complex regulates also defense signaling pathways. On the other hand, we show new data on AtGRP3-overexpressing plants indicating that its role in aluminum signaling pathways, as previously observed for elicitor signaling, seems to be more complex than a simple negative regulator...
January 26, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/28122427/familiar-hyperekplexia-a-potential-cause-of-cautious-gait-a-new-korean-case-and-a-systematic-review-of-phenotypes
#15
Yoonju Lee, Nan Young Kim, Sangkyoon Hong, Su Jin Chung, Seong Ho Jeong, Phil Hyu Lee, Young H Sohn
Familial hyperekplexia, also called startle disease, is a rare neurological disorder characterized by excessive startle responses to noise or touch. It can be associated with serious injury from frequent falls, apnea spells, and aspiration pneumonia. Familial hyperekplexia has a heterogeneous genetic background with several identified causative genes; it demonstrates both dominant and recessive inheritance in the α1 subunit of the glycine receptor (GLRA1), the β subunit of the glycine receptor and the presynaptic sodium and chloride-dependent glycine transporter 2 genes...
January 2017: Journal of Movement Disorders
https://www.readbyqxmd.com/read/28121133/probing-the-structural-mechanism-of-partial-agonism-in-glycine-receptors-using-the-fluorescent-artificial-amino-acid-anap
#16
Ming S Soh, Argel Estrada-Mondragon, Nela Durisic, Angelo Keramidas, Joseph W Lynch
The efficacy of an agonist at a pentameric ligand-gated ion channel is determined by the rate at which it induces a conformational change from the resting closed state to a preopen ("flip") state. If the ability of an agonist to promote this isomerization is sufficiently low, then it becomes a partial agonist. As partial agonists at pentameric ligand-gated ion channels show considerable promise as therapeutics, understanding the structural basis of the resting-flip-state isomerization may provide insight into therapeutic design...
February 2, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28114971/molecular-alterations-in-skeletal-muscle-in-rheumatoid-arthritis-are-related-to-disease-activity-physical-inactivity-and-disability
#17
Kim M Huffman, Ryan Jessee, Brian Andonian, Brittany N Davis, Rachel Narowski, Janet L Huebner, Virginia B Kraus, Julie McCracken, Brian F Gilmore, K Noelle Tune, Milton Campbell, Timothy R Koves, Deborah M Muoio, Monica J Hubal, William E Kraus
BACKGROUND: To identify molecular alterations in skeletal muscle in rheumatoid arthritis (RA) that may contribute to ongoing disability in RA. METHODS: Persons with seropositive or erosive RA (n = 51) and control subjects matched for age, gender, race, body mass index (BMI), and physical activity (n = 51) underwent assessment of disease activity, disability, pain, physical activity and thigh muscle biopsies. Muscle tissue was used for measurement of pro-inflammatory markers, transcriptomics, and comprehensive profiling of metabolic intermediates...
January 23, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28112257/ethylene-response-pathway-modulates-attractiveness-of-plant-roots-to-soybean-cyst-nematode-heterodera-glycines
#18
Yanfeng Hu, Jia You, Chunjie Li, Valerie M Williamson, Congli Wang
Plant parasitic nematodes respond to root exudates to locate their host roots. In our studies second stage juveniles of Heterodera glycines, the soybean cyst nematode (SCN), quickly migrated to soybean roots in Pluronic F-127 gel. Roots of soybean and non-host Arabidopsis treated with the ethylene (ET)-synthesis inhibitor aminoethoxyvinylglycine (AVG) were more attractive to SCN than untreated roots, and significantly more nematodes penetrated into roots. Moreover, Arabidopsis ET insensitive mutants (ein2, ein2-1, ein2-5, ein3-1, ein5-1, and ein6) were more attractive than wild-type plants...
January 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28110076/facilitation-of-distinct-inhibitory-synaptic-inputs-by-chemical-anoxia-in-neurons-in-the-oculomotor-facial-and-hypoglossal-motor-nuclei-of-the-rat
#19
Satoshi Takagi, Yu Kono, Masashi Nagase, Soichiro Mochio, Fusao Kato
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the selective loss of motor neurons in the brainstem and spinal cord. Clinical studies have indicated that there is a distinct region-dependent difference in the vulnerability of motor neurons. For example, the motor neurons in the facial and hypoglossal nuclei are more susceptible to neuronal death than those in the oculomotor nucleus. To understand the mechanism underlying the differential susceptibility to cell death of the neurons in different motor nuclei, we compared the effects of chemical anoxia on the membrane currents and postsynaptic currents in different motor nuclei...
January 19, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28105280/glun2a-selective-pyridopyrimidinone-series-of-nmdar-positive-allosteric-modulators-with-an-improved-in-vivo-profile
#20
Elisia Villemure, Matthew Volgraf, Yu Jiang, Guosheng Wu, Cuong Q Ly, Po-Wai Yuen, Aijun Lu, Xifeng Luo, Mingcui Liu, Shun Zhang, Patrick J Lupardus, Heidi J A Wallweber, Bianca M Liederer, Gauri Deshmukh, Emile Plise, Suzanne Tay, Tzu-Ming Wang, Jesse E Hanson, David H Hackos, Kimberly Scearce-Levie, Jacob B Schwarz, Benjamin D Sellers
The N-methyl-d-aspartate receptor (NMDAR) is an ionotropic glutamate receptor, gated by the endogenous coagonists glutamate and glycine, permeable to Ca(2+) and Na(+). NMDAR dysfunction is associated with numerous neurological and psychiatric disorders, including schizophrenia, depression, and Alzheimer's disease. Recently, we have disclosed GNE-0723 (1), a GluN2A subunit-selective and brain-penetrant positive allosteric modulator (PAM) of NMDARs. This work highlights the discovery of a related pyridopyrimidinone core with distinct structure-activity relationships, despite the structural similarity to GNE-0723...
January 12, 2017: ACS Medicinal Chemistry Letters
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