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https://www.readbyqxmd.com/read/28821660/contribution-of-astroglial-cx43-hemichannels-to-the-modulation-of-glutamatergic-currents-by-d-serine-in-the-mouse-prefrontal-cortex
#1
Claire Meunier, Nan Wang, Chenju Yi, Glenn Dallerac, Pascal Ezan, Annette Koulakoff, Luc Leybaert, Christian Giaume
Astrocytes interact dynamically with neurons by modifying synaptic activity and plasticity. This interplay occurs through a process named gliotransmission, meaning that neuroactive molecules are released by astrocytes. Acting as a gliotransmitter, D-serine co-agonist of the NMDA receptor at the glycine binding site, can be released by astrocytes in a calcium [Ca(2+)]i-dependent manner. A typical feature of astrocytes is their high expression level of connexin43 (Cx43), a protein forming gap junction channels and hemichannels associated with dynamic neuroglial interactions...
August 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28816240/rodent-mismatch-negativity-mmn-theta-neuro-oscillatory-response-as-a-translational-neurophysiological-biomarker-for-n-methyl-d-aspartate-receptor-based-new-treatment-development-in-schizophrenia
#2
Migyung Lee, Andrea Balla, Henry Sershen, Pejman Sehatpour, Peter Lakatos, Daniel C Javitt
Deficits in the generation of auditory mismatch negativity (MMN) generation are among the most widely replicated neurophysiological abnormalities in schizophrenia and linked to underlying dysfunction of N-methyl-D-aspartate receptor (NMDAR)-mediated neurotransmission. Here, we evaluate physiological properties of rodent MMN, along with sensitivity to NMDAR agonist and antagonist treatment, relative to known patterns of dysfunction in schizophrenia. Epidural neurophysiological responses to frequency- and duration-deviants, along with responses to standard stimuli, were obtained at baseline and following 2 and 4 weeks treatment from rats treated with saline, phencyclidine (PCP, 15 mg/kg/d by osmotic minipump), or PCP+glycine (16% by weight diet) interventions...
August 17, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28814518/a-single-amino-acid-substitution-at-position-225-in-ha-alters-the-transmissibility-of-eurasian-avian-like-h1n1-swine-influenza-virus-in-guinea-pigs
#3
Zeng Wang, Huanliang Yang, Yan Chen, Shiyu Tao, Liling Liu, Huihui Kong, Shujie Ma, Fei Meng, Yasuo Suzuki, Chuanling Qiao, Hualan Chen
Efficient transmission from human to human is the prerequisite for an influenza virus to cause a pandemic; however, the molecular determinants of influenza virus transmission are still largely unknown. In this study, we explored the molecular basis for transmission of Eurasian avian-like H1N1 (EAH1N1) swine influenza viruses by comparing two viruses that are genetically similar but differ in their transmissibility in guinea pigs: the A/swine/Guangxi/18/2011 virus (GX/18) is highly transmissible by respiratory droplet in guinea pigs, whereas the A/swine/Heilongjiang/27/2012 virus (HLJ/27) does not transmit in this animal model...
August 16, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28807745/acute-toxicity-of-functionalized-single-wall-carbon-nanotubes-a-biochemical-histopathologic-and-proteomics-approach
#4
Homa Ahmadi, Mohammad Ramezani, Rezvan Yazdian Robati, Behzad Behnam, Kamal Razavi Azarkhiavi, Azadeh Hashem Nia, Ahad Mokhtarzadeh, Maryam Matbou Riahi, Bibi Marjan Razavi, Khalil Abnous
Recently carbon nanotubes (CNTs) showed promising potentials in different biomedical applications but their safe use in humans and probable toxicities are still challenging. The aim of this study was to determine the acute toxicity of functionalized single walled carbon nanotubes (SWCNTs). In this project, PEGylated and Tween functionalized SWCNTs were prepared. BALB/c mice were randomly divided into nine groups, including PEGylated SWCNTs (75,150μg/mouse) and PEG, Tween80 suspended SWCNTs, Tween 80 and a control group (intact mice)...
August 11, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28804557/motor-neuron-degeneration-following-glycine-mediated-excitotoxicity-induces-spastic-paralysis-after-spinal-cord-ischemia-reperfusion-injury-in-rabbit
#5
Li Wang, Sen Li, Yuan Liu, Dong-Liang Feng, Long Jiang, Zai-Yun Long, Ya-Min Wu
Spinal cord ischemia and reperfusion (SCIR) injury is the major cause of a wide range of complications, including neural degeneration and devastating paraplegia. Decrease of inhibitory neurotransmitters and increase of excitory neurotransmitters are the major cause for the excitotoxicity of neurons. However, no study has reported the temporal loss of motor neuron in the ventral horn of spinal cord area following SCIR-induced spastic paralysis, not even the mechanism under it. In the present study, we found that the rabbits were mainly spastic paralyzed after spinal cord ischemia-reperfusion injury...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28791779/crystal-structure-of-the-xpo1p-nuclear-export-complex-bound-to-the-sxfg-pxfg-repeats-of-the-nucleoporin-nup42p
#6
Masako Koyama, Hidemi Hirano, Natsuki Shirai, Yoshiyuki Matsuura
Xpo1p (yeast CRM1) is the major nuclear export receptor that carries a plethora of proteins and ribonucleoproteins from the nucleus to cytoplasm. The passage of the Xpo1p nuclear export complex through nuclear pore complexes (NPCs) is facilitated by interactions with nucleoporins (Nups) containing extensive repeats of phenylalanine-glycine (so-called FG repeats), although the precise role of each Nup in the nuclear export reaction remains incompletely understood. Here we report structural and biochemical characterization of the interactions between the Xpo1p nuclear export complex and the FG repeats of Nup42p, a nucleoporin localized at the cytoplasmic face of yeast NPCs and has characteristic SxFG/PxFG sequence repeat motif...
August 8, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/28791431/glycine-receptors-and-glycine-transporters-targets-for-novel-analgesics
#7
REVIEW
Hanns Ulrich Zeilhofer, Mario A Acuña, Jacinthe Gingras, Gonzalo E Yévenes
Glycinergic neurotransmission has long been known for its role in spinal motor control. During the last two decades, additional functions have become increasingly recognized-among them is a critical contribution to spinal pain processing. Studies in rodent pain models provide proof-of-concept evidence that enhancing inhibitory glycinergic neurotransmission reduces chronic pain symptoms. Apparent strategies for pharmacological intervention include positive allosteric modulators of glycine receptors and modulators or inhibitors of the glial and neuronal glycine transporters GlyT1 and GlyT2...
August 8, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28790330/the-matrikine-acetylated-proline-glycine-proline-couples-vascular-inflammation-and-acute-cardiac-rejection
#8
Gregory A Payne, Jindong Li, Xin Xu, Patricia Jackson, Hongwei Qin, David M Pollock, J Michael Wells, Suzanne Oparil, Massoud Leesar, Rakesh P Patel, J Edwin Blalock, Amit Gaggar
The extracellular matrix (ECM) is a dynamic, bioactive structure critical to organ development, structure and function. Excessive remodeling of the ECM is a hallmark of a variety of inflammatory conditions including vascular disease. Endothelin-1 (ET1) synthesis is understood to promote cardiovascular diseases including acute cardiac transplant rejection; however, the contribution of ECM-derived chemokines (matrikines) to vascular inflammation remains poorly understood. Herein we report that the matrikine acetylated Pro-Gly-Pro (PGP) stimulates vascular inflammation through activation of endothelial CXC Chemokine Receptor 2 (CXCR2) and production of endothelin-1 both in vitro and in vivo...
August 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28780732/assessment-of-the-target-engagement-and-d-serine-biomarker-profiles-of-the-d-amino-acid-oxidase-inhibitors-sodium-benzoate-and-pgm030756
#9
Eimear Howley, Michael Bestwick, Rosa Fradley, Helen Harrison, Mathew Leveridge, Kengo Okada, Charlotte Fieldhouse, Will Farnaby, Hannah Canning, Andy P Sykes, Kevin Merchant, Katherine Hazel, Catrina Kerr, Natasha Kinsella, Louise Walsh, David G Livermore, Isaac Hoffman, Jonathan Ellery, Phillip Mitchell, Toshal Patel, Mark Carlton, Matt Barnes, David J Miller
Irregular N-methyl-D-aspartate receptor (NMDAR) function is one of the main hypotheses employed to facilitate understanding of the underlying disease state of schizophrenia. Although direct agonism of the NMDAR has not yielded promising therapeutics, advances have been made by modulating the NMDAR co-agonist site which is activated by glycine and D-serine. One approach to activate the co-agonist site is to increase synaptic D-serine levels through inhibition of D-amino acid oxidase (DAO), the major catabolic clearance pathway for this and other D-amino acids...
August 5, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28774887/suppressed-hepatic-bile-acid-signalling-despite-elevated-production-of-primary-and-secondary-bile-acids-in-nafld
#10
Na Jiao, Susan S Baker, Adrian Chapa-Rodriguez, Wensheng Liu, Colleen A Nugent, Maria Tsompana, Lucy Mastrandrea, Michael J Buck, Robert D Baker, Robert J Genco, Ruixin Zhu, Lixin Zhu
OBJECTIVE: Bile acids are regulators of lipid and glucose metabolism, and modulate inflammation in the liver and other tissues. Primary bile acids such as cholic acid and chenodeoxycholic acid (CDCA) are produced in the liver, and converted into secondary bile acids such as deoxycholic acid (DCA) and lithocholic acid by gut microbiota. Here we investigated the possible roles of bile acids in non-alcoholic fatty liver disease (NAFLD) pathogenesis and the impact of the gut microbiome on bile acid signalling in NAFLD...
August 3, 2017: Gut
https://www.readbyqxmd.com/read/28771403/structural-insight-into-the-activation-of-a-class-b-g-protein-coupled-receptor-by-peptide-hormones-in-live-human-cells
#11
Lisa Seidel, Barbara Zarzycka, Saheem A Zaidi, Vsevolod Katritch, Irene Coin
The activation mechanism of class B G-protein-coupled receptors (GPCRs) remains largely unknown. To characterize conformational changes induced by peptide hormones, we investigated interactions of the class B corticotropin-releasing factor receptor type 1 (CRF1R) with two peptide agonists and three peptide antagonists obtained by N-truncation of the agonists. Surface mapping with genetically encoded photo-crosslinkers and pair-wise crosslinking revealed distinct footprints of agonists and antagonists on the transmembrane domain (TMD) of CRF1R and identified numerous ligand-receptor contact sites, directly from the intact receptor in live human cells...
August 3, 2017: ELife
https://www.readbyqxmd.com/read/28762314/insights-into-nicotinic-receptor-signaling-in-nicotine-addiction-implications-for-prevention-and-treatment
#12
Wuyi Liu, Ming D Li
Nicotinic acetylcholine receptors (nAChRs) belong to the Cys-loop ligand-gated ion-channel (LGIC) superfamily, which also includes the GABA, glycine, and serotonin receptors. Many nAChR subunits have been identified and shown to be involved in signal transduction on binding to them of either the neurotransmitter acetylcholine or exogenous ligands such as nicotine. The nAChRs are pentameric assemblies of homologous subunits surrounding a central pore that gates cation flux, and they are expressed at neuromuscular junctions throughout the nervous system...
August 1, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28760974/structural-basis-of-subunit-selectivity-for-competitive-nmda-receptor-antagonists-with-preference-for-glun2a-over-glun2b-subunits
#13
Genevieve E Lind, Tung-Chung Mou, Lucia Tamborini, Martin G Pomper, Carlo De Micheli, Paola Conti, Andrea Pinto, Kasper B Hansen
NMDA-type glutamate receptors are ligand-gated ion channels that contribute to excitatory neurotransmission in the central nervous system (CNS). Most NMDA receptors comprise two glycine-binding GluN1 and two glutamate-binding GluN2 subunits (GluN2A-D). We describe highly potent (S)-5-[(R)-2-amino-2-carboxyethyl]-4,5-dihydro-1H-pyrazole-3-carboxylic acid (ACEPC) competitive GluN2 antagonists, of which ST3 has a binding affinity of 52 nM at GluN1/2A and 782 nM at GluN1/2B receptors. This 15-fold preference of ST3 for GluN1/2A over GluN1/2B is improved compared with NVP-AAM077, a widely used GluN2A-selective antagonist, which we show has 11-fold preference for GluN1/2A over GluN1/2B...
August 15, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28758885/dimensional-traits-of-schizotypy-associated-with-glycine-receptor-glra1-polymorphism-an-exploratory-candidate-gene-association-study
#14
Anvi K Vora, Amanda M Fisher, Antonia S New, Erin A Hazlett, Margaret McNamara, Qiaoping Yuan, Zhifeng Zhou, Colin Hodgkinson, David Goldman, Larry J Siever, Panos Roussos, M Mercedes Perez-Rodriguez
Schizotypy captures the underlying genetic vulnerability to schizophrenia. However, the genetic underpinnings of schizotypy remain unexplored. The authors examined the relationship between single nucleotide polymorphisms (SNPs) and schizotypy. A sample of 137 subjects (43 healthy controls, 34 subjects with schizotypal personality disorder [SPD], 32 with borderline personality disorder, and 25 with other personality disorders) completed the Schizotypal Personality Questionnaire (SPQ). Subjects were genotyped using a custom array chip...
July 31, 2017: Journal of Personality Disorders
https://www.readbyqxmd.com/read/28758414/modulation-of-n-methyl-d-aspartate-receptors-in-isolated-rat-heart
#15
Ivan M Srejovic, Vladimir I Zivkovic, Tamara R Nikolic, Nevena Jeremic, Isidora Stojic, Jovana Jeremic, Dragan Djuric, Vladimir Jakovljevic
Considering the limited data about the role of N-methyl-D-aspartate receptors (NMDA-R) in cardiovascular system and heart, the aim of the present study was to examine the effects of NMDA and DL-homocysteine thiolacotne (DL-Hcy TLHC), alone and in combinations with glycine, memantine and ifenprodil, in the isolated rat heart. The hearts of Wistar albino rats were retrogradely perfused according to the Langendorff technique at a constant perfusion pressure. The experimental protocol for all experimental groups included the stabilization period, application of estimated substance in duration of 5 minutes, followed by wash-out period in duration of 10 minutes...
July 30, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28749574/design-synthesis-pharmacological-evaluation-and-docking-studies-of-glun2b-selective-nmda-receptor-antagonists-with-a-benzo-7-annulen-7-amine-scaffold
#16
Sandeep Gawaskar, Louisa Temme, Julian A Schreiber, Dirk Schepmann, Alessandro Bonifazi, Dina Robaa, Wolfgang Sippl, Nathalie Strutz-Seebohm, Guiscard Seebohm, Bernhard Wünsch
Antagonists that selectively target GluN2B-subunit-containing N-methyl-d-aspartate (NMDA) receptors are of major interest for the treatment of various neurological disorders. In this study, relationships between variously substituted benzo[7]annulen-7-amines and their GluN2B affinity were investigated. 2-Nitro-5,6,8,9-tetrahydrobenzo[7]annulen-7-one (8) represents the central building block for the introduction of various substituents at the 2-position and various 7-amino moieties. N-(3-Phenylpropyl)-6,7,8,9-tetrahydro-5H-benzo[7]annulen-7-amines with a 2-NO2 (7 c), 2-Cl (15 c), or 2-OBn group (22 c) show very high GluN2B affinity (Ki =1...
July 27, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28748374/alterations-in-amino-acid-levels-in-mouse-brain-regions-after-adjunctive-treatment-of-brexpiprazole-with-fluoxetine-comparison-with-r-ketamine
#17
Min Ma, Qian Ren, Yuko Fujita, Chun Yang, Chao Dong, Yuta Ohgi, Takashi Futamura, Kenji Hashimoto
RATIONALE: Brexpiprazole, a serotonin-dopamine activity modulator, is approved in the USA as an adjunctive therapy to antidepressants for treating major depressive disorders. Similar to the N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine, the combination of brexpiprazole and fluoxetine has demonstrated antidepressant-like effects in animal models of depression. OBJECTIVES: The present study was conducted to examine whether the combination of brexpiprazole and fluoxetine could affect the tissue levels of amino acids [glutamate, glutamine, γ-aminobutyric acid (GABA), D-serine, L-serine, and glycine] that are associated with NMDAR neurotransmission...
July 26, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28747658/a-single-amino-acid-substitution-confers-b-cell-clonogenic-activity-to-the-hiv-1-matrix-protein-p17
#18
Cinzia Giagulli, Pasqualina D'Ursi, Wangxiao He, Simone Zorzan, Francesca Caccuri, Kristen Varney, Alessandro Orro, Stefania Marsico, Benoît Otjacques, Carlo Laudanna, Luciano Milanesi, Riccardo Dolcetti, Simona Fiorentini, Wuyuan Lu, Arnaldo Caruso
Recent data highlight the presence, in HIV-1-seropositive patients with lymphoma, of p17 variants (vp17s) endowed with B-cell clonogenicity, suggesting a role of vp17s in lymphomagenesis. We investigated the mechanisms responsible for the functional disparity on B cells between a wild-type p17 (refp17) and a vp17 named S75X. Here, we show that a single Arginine (R) to Glycine (G) mutation at position 76 in the refp17 backbone (p17R76G), as in the S75X variant, is per se sufficient to confer a B-cell clonogenic potential to the viral protein and modulate, through activation of the PTEN/PI3K/Akt signaling pathway, different molecules involved in apoptosis inhibition (CASP-9, CASP-7, DFF-45, NPM, YWHAZ, Src, PAX2, MAPK8), cell cycle promotion and cancer progression (CDK1, CDK2, CDK8, CHEK1, CHEK2, GSK-3 beta, NPM, PAK1, PP2C-alpha)...
July 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28744152/pharmacodynamic-genetic-polymorphisms-affect-adverse-drug-reactions-of-haloperidol-in-patients-with-alcohol-use-disorder
#19
Mikhail Sergeevich Zastrozhin, Vadim Markovich Brodyansky, Valentin Yurievich Skryabin, Elena Anatolievna Grishina, Dmitry Vladimirovich Ivashchenko, Kristina Anatolievna Ryzhikova, Ludmila Mikhaylovna Savchenko, Alexander Olegovich Kibitov, Evgeny Alekseevich Bryun, Dmitry Alekseevich Sychev
BACKGROUND: Antipsychotic action of haloperidol is due to blockade of D2 receptors in the mesolimbic dopamine pathway, while the adverse drug reactions are associated with striatal D2 receptor blockade. Contradictory data concerning the effects of genetic polymorphisms of genes encoding these receptors and associated structures (catechol-O-methyltransferase [COMT], glycine transporter and gene encoding the density of D2 receptors on the neuronal membrane) are described. OBJECTIVE: The objectives of this study were to evaluate the correlation between DRD2, SLC6A3 (DAT) and COMT genetic polymorphisms and to investigate their effect on the development of adverse drug reactions in patients with alcohol-use disorder who received haloperidol...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28739483/structural-modeling-for-the-open-state-of-an-nmda-receptor
#20
Xiaodong Pang, Huan-Xiang Zhou
NMDA receptors are tetrameric ligand-gated ion channels that are crucial for neurodevelopment and higher order processes such as learning and memory, and have been implicated in numerous neurological disorders. The lack of a structure for the channel open state has greatly hampered the understanding of the normal gating process and mechanisms of disease-associated mutations. Here we report the structural modeling for the open state of an NMDA receptor. Staring from the crystal structure of the closed state, we repacked the pore-lining helices to generate an initial open model...
July 22, 2017: Journal of Structural Biology
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