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Metabotropic glutamate receptor

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https://www.readbyqxmd.com/read/28646617/melanoma-associated-grm3-variants-dysregulate-melanosome-trafficking-and-camp-signaling
#1
Ana Neto, Craig J Ceol
Large-scale sequencing studies have revealed several genes that are recurrently mutated in melanomas. To annotate the melanoma genome we have expressed tumor-associated variants of these genes in zebrafish and characterized their effects on melanocyte development and function. Here, we describe expression of tumor-associated variants of the recurrently-mutated metabotropic glutamate receptor 3 (GRM3) gene. Unlike wild-type GRM3, tumor-associated GRM3 variants disrupted trafficking of melanosomes, causing their aggregation in the cell body...
June 24, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/28646511/control-of-autoimmune-inflammation-using-liposomes-to-deliver-positive-allosteric-modulators-of-metabotropic-glutamate-receptors
#2
Joshua M Gammon, Arjun R Adapa, Christopher M Jewell
Multiple sclerosis (MS) is an autoimmune disease where myelin is incorrectly recognized as foreign and attacked by the adaptive immune system. Dendritic cells (DCs) direct adaptive immunity by presenting antigens to T cells, therefore serving as a target for autoimmune therapies. N-Phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide (PHCCC), a positive allosteric modulator of metabotropic glutamate receptor 4 (mGluR4), can promote regulatory T cells by altering cytokine secretion to bias T cell differentiation...
June 24, 2017: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/28645622/in-vivo-effects-of-knocking-down-metabotropic-glutamate-receptor-5-in-the-sod1-g93a-mouse-model-of-amyotrophic-lateral-sclerosis
#3
Tiziana Bonifacino, Luca Cattaneo, Elena Gallia, Aldamaria Puliti, Marcello Melone, Francesca Provenzano, Simone Bossi, Ilaria Musante, Cesare Usai, Fiorenzo Conti, Giambattista Bonanno, Marco Milanese
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder due to loss of upper and lower motor neurons (MNs). The mechanisms of neuronal death are largely unknown, thus prejudicing the successful pharmacological treatment. One major cause for MN degeneration in ALS is represented by glutamate(Glu)-mediated excitotoxicity. We have previously reported that activation of Group I metabotropic Glu receptors (mGluR1 and mGluR5) at glutamatergic spinal cord nerve terminals produces abnormal Glu release in the widely studied SOD1(G93A) mouse model of ALS...
June 20, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28642149/activated-mglur5-protects-bv2-cells-against-ogd-r-induced-cytotoxicity-by-modulating-bdnf-trkb-pathway
#4
Xinchun Ye, Lu Yu, Dandan Zuo, Liang Zhang, Jie Zu, Jinxia Hu, Jiao Tang, Lei Bao, Chengcheng Cui, Ruixue Zhang, Guoliang Jin, Kun Zan, Zuohui Zhang, Xinxin Yang, Hongjuan Shi, Zunsheng Zhang, Qihua Xiao, Yonghai Liu, Jie Xiang, Xueling Zhang, Guiyun Cui
Activated Metabotropic glutamate receptors 5(mGluR5) exhibits protective effects against ischemic brain damage, but the underlying mechanisms are not clearly known. Brain-derived neurotrophic factor (BDNF), as a valuable member of neurotrophic factor family, exerts its protection by combining with its high-affinity receptor tyrosine protein kinase B (TrkB). To investigate the role of activated mGluR5 against oxygen-glucose deprivation (OGD)/reoxygenation (R)-mediated cytotoxicity, the cell viability, apoptosis, the release of inflammatory cytokines and accumulation of reactive oxygen species (ROS) were evaluated in BV2 cells (Microglia cell line) with or without OGD/R exposure...
June 19, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28631520/striatal-changes-underlie-mpep-mediated-suppression-of-the-acquisition-and-expression-of-pramipexole-induced-place-preference-in-an-alpha-synuclein-rat-model-of-parkinson-s-disease
#5
Simon Loiodice, Portia McGhan, Vitalina Gryshkova, Renaud Fleurance, David Dardou, Aziz Hafidi, Andre Nogueira da Costa, Franck Durif
Impulsive-compulsive disorders in Parkinson's disease patients have been described as behavioural or substance addictions including pathological gambling or compulsive medication use of dopamine replacement therapy. A substantial gap remains in the understanding of these disorders. We previously demonstrated that the rewarding effect of the D2/D3 agonist pramipexole was enhanced after repeated exposure to L-dopa and alpha-synuclein mediated dopaminergic nigral loss with specific transcriptional signatures suggesting a key involvement of the glutamatergic pathway...
June 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28629846/hippocampal-gr-and-cb1-mediated-mglur5-differentially-produces-susceptibility-and-resilience-to-acute-and-chronic-mild-stress-in-rats
#6
Hongli Sun, Rujuan Su, Xiaoxiao Zhang, Jun Wen, Dan Yao, Xinru Gao, Zhongliang Zhu, Hui Li
The molecular mechanism of individual response of susceptibility and resilience under psychological stress remains controversial and unclear. The present study aimed to explore the relationship of metabotropic glutamate receptor 5 (mGluR5) with glucocorticoid receptor (GR) or cannabinoid receptor (CB1) and further indicate the molecular mechanism of susceptibility and resilience to acute stress (AS) and chronic mild stress (CMS). Sucrose preference test and open field test were used to evaluate the response of susceptibility and resilience under stress in rats...
June 16, 2017: Neuroscience
https://www.readbyqxmd.com/read/28624317/modulatory-effects-of-ampicillin-sulbactam-on-glial-glutamate-transporters-and-metabotropic-glutamate-receptor-1-as-well-as-reinstatement-to-cocaine-seeking-behavior
#7
Alaa M Hammad, Fawaz Alasmari, Yusuf S Althobaiti, Youssef Sari
Glutamatergic system has an important role in cocaine-seeking behavior. Studies have reported that chronic exposure to cocaine induces downregulation of glutamate transporter-1 (GLT-1) and cystine/glutamate exchanger (xCT) in the central reward brain regions. Ceftriaxone, a β-lactam antibiotic, restored GLT-1 expression and consequently reduced cue-induced reinstatement of cocaine-seeking behavior. In this study, we investigated the reinstatement to cocaine (20mg/kg, i.p.) seeking behavior using a conditioned place preference (CPP) paradigm in male alcohol-preferring (P) rats...
June 15, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28621704/sensitization-of-trpv1-and-trpa1-via-peripheral-mglur5-signaling-contributes-to-thermal-and-mechanical-hypersensitivity
#8
Kuniya Honda, Masamichi Shinoda, Masahiro Kondo, Kohei Shimizu, Hisashi Yonemoto, Katsuhiko Otsuki, Ryuta Akasaka, Akihiko Furukawa, Koichi Iwata
Peripheral tissue inflammation or injury causes glutamate release from nociceptive axons, keratinocytes and Schwann cells, resulting in thermal hypersensitivity. However, the detailed molecular mechanisms underlying glutamate-induced thermal hypersensitivity are unknown. The aim of this study was to clarify the involvement of peripheral transient receptor potential (TRP) ankyrin 1 (TRPA1), TRP vanilloid 1 (TRPV1) and protein kinase C epsilon (PKCε) in glutamate-induced pain hypersensitivity. The amount of glutamate in the facial tissue was significantly increased 3 days after facial CFA injection...
June 8, 2017: Pain
https://www.readbyqxmd.com/read/28615682/improved-retinal-function-in-rcs-rats-after-suppressing-the-over-activation-of-mglur5
#9
Jiaman Dai, Yan Fu, Yuxiao Zeng, Shiying Li, Zheng Qin Yin
Müller cells maintain retinal synaptic homeostasis by taking up glutamate from the synaptic cleft and transporting glutamine back to the neurons. To study the interaction between Müller cells and photoreceptors, we injected either DL-α-aminoadipate or L-methionine sulfoximine-both inhibitors of glutamine synthetase-subretinally in rats. Following injection, the a-wave of the electroretinogram (ERG) was attenuated, and metabotropic glutamate receptor 5 (mGluR5) was activated. Selective antagonism of mGluR5 by 2-methyl-6-(phenylethynyl)-pyridine increased the ERG a-wave amplitude and also increased rhodopsin expression...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28615627/reduction-in-migratory-phenotype-in-a-metastasized-breast-cancer-cell-line-via-downregulation-of-s100a4-and-grm3
#10
Andy Chen, Luqi Wang, Bai-Yan Li, Jesse Sherman, Jong E Ryu, Kazunori Hamamura, Yunlong Liu, Harikrishna Nakshatri, Hiroki Yokota
To investigate phenotypic and genotypic alterations before and after bone metastasis, we conducted genome-wide mRNA profiling and DNA exon sequencing of two cell lines (TMD and BMD) derived from a mouse xenograft model. TMD cells were harvested from the mammary fat pad after transfecting MDA-MB-231 breast cancer cells, while BMD cells were isolated from the metastasized bone. Compared to BMD cells, TMD cells exhibited higher cellular motility. In contrast, BMD cells formed a spheroid with a smoother and more circular surface when co-cultured with osteoblasts...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28605494/glutamate-transport-a-new-bench-to-bedside-mechanism-for-treating-drug-abuse
#11
Sade Spencer, Peter W Kalivas
Drug addiction has often been described as a "hijacking" of the brain circuits involved in learning and memory. Glutamate is the principal excitatory neurotransmitter in the brain, and its contribution to synaptic plasticity and learning processes is well established in animal models. Likewise, over the past twenty years the addiction field has ascribed a critical role for glutamatergic transmission in the development of addiction. Chronic drug use produces enduring neuroadaptations in corticostriatal projections that are believed to contribute to a maladaptive deficit in inhibitory control over behavior...
June 12, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28591718/riluzole-exerts-distinct-antitumor-effects-from-a-metabotropic-glutamate-receptor-1-specific-inhibitor-on-breast-cancer-cells
#12
Sonia C Dolfi, Daniel J Medina, Aparna Kareddula, Bhavna Paratala, Ashley Rose, Jatinder Dhami, Suzie Chen, Shridar Ganesan, Gillian Mackay, Alexei Vazquez, Kim M Hirshfield
Recent evidence suggests that glutamate signaling plays an important role in cancer. Riluzole is a glutamate release inhibitor and FDA-approved drug for the treatment of amyotrophic lateral sclerosis. It has been investigated as an inhibitor of cancer cell growth and tumorigenesis with the intention of repurposing it for the treatment of cancer. Riluzole is thought to act by indirectly inhibiting glutamate signaling. However, the specific effects of riluzole in breast cancer cells are not well understood. In this study, the anti-cancer effects of riluzole were explored in a panel of breast cancer cell lines in comparison to the metabotropic glutamate receptor 1-specific inhibitor BAY 36-7620...
May 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28571823/synthesis-and-in-vitro-evaluation-of-three-novel-radiotracers-for-imaging-of-metabotropic-glutamate-receptor-subtype-2-in-rat-brain
#13
Katsushi Kumata, Tomoteru Yamasaki, Akiko Hatori, Yiding Zhang, Wakana Mori, Masayuki Fujinaga, Lin Xie, Takayuki Okubo, Nobuki Nengaki, Ming-Rong Zhang
The purpose of this study was to develop three new radiotracers, 1-(cyclopropylmethyl)-4-([(11)C/(18)F]substituted-phenyl)piperidin-1-yl-2-oxo-1,2-dihydropyridine-3-carbonitrile ([(11)C]1, [(11)C]2, and [(18)F]4), and to examine their specific bindings with metabotropic glutamate receptor subtype 2 (mGluR2) in rat brain sections by using in vitro autoradiography. These compounds were found to possess potent in vitro binding affinities (Ki: 8.0-34.1nM) for mGluR2 in rat brain homogenate. [(11)C]1, [(11)C]2, and [(18)F]4 were synthesized by [(11)C/(18)F]alkylation of the corresponding phenol precursors with [(11)C]methyl iodide or [(18)F]fluoroethyl bromide with >98% radiochemical purity and 80-130GBq/μmol specific activity at the end of synthesis...
May 23, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28570324/neurologic-complications-of-lymphoma-leukemia-and-paraproteinemias
#14
Michelle L Mauermann
PURPOSE OF REVIEW: This article reviews the spectrum of neurologic complications associated with lymphoma, leukemia, and paraproteinemic disorders. While leptomeningeal metastasis is the most common complication of lymphoma and leukemia and peripheral neuropathy is the most common complication of paraproteinemic disorders, clinicians need to be familiar with the diverse neurologic complications of these disorders. RECENT FINDINGS: Lymphomatous nervous system involvement can be difficult to diagnose, especially when it is the presenting symptom...
June 2017: Continuum: Lifelong Learning in Neurology
https://www.readbyqxmd.com/read/28569048/astrocyte-mediated-synapse-remodeling-in-the-pathological-brain
#15
REVIEW
Sun Kwang Kim, Junichi Nabekura, Schuichi Koizumi
Astrocytes, a major type of glia, reciprocally influence synaptic transmission and connectivity, forming the "tripartite synapses". Astrocytic metabotropic glutamate receptor (mGluR)-mediated Ca(2+) waves and release of gliotransmitters or synaptogenic molecules mediate this neuron-glia interaction in the developing brain, but this signaling has been challenged for adult brain. However, cumulative evidence has suggested that mature astrocytes exhibit re-awakening of such immature phenotype in the pathological adult brain...
June 1, 2017: Glia
https://www.readbyqxmd.com/read/28565908/synthesis-and-preliminary-studies-of-a-novel-negative-allosteric-modulator-11-c-qca-for-imaging-of-metabotropic-glutamate-receptor-2
#16
Xiaofei Zhang, Katsushi Kumata, Tomoteru Yamasaki, Ran Cheng, Akiko Hatori, Longle Ma, Yiding Zhang, Lin Xie, Lu Wang, Hye Jin Kang, Douglas J Sheffler, Nicholas D P Cosford, Ming-Rong Zhang, Steven H Liang
Metabotropic glutamate 2 receptors (mGlu2) are involved in the pathogenesis of several CNS disorders and neurodegenerative diseases. Pharmacological modulation of this target represents a potential disease-modifying approach for the treatment of substance abuse, depression, schizophrenia and dementias. While quantification of mGlu2 receptors in the living brain by positron emission tomography (PET) would help us better understand signaling pathways relevant to these conditions, few successful examples have been demonstrated to image mGlu2 in vivo and a suitable PET tracer is yet to be identified...
May 31, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28560482/integrated-in-silico-fragment-based-drug-design-case-study-with-allosteric-modulators-on-metabotropic-glutamate-receptor-5
#17
Yuemin Bian, Zhiwei Feng, Peng Yang, Xiang-Qun Xie
GPCR allosteric modulators target at the allosteric binding pockets of G protein-coupled receptors (GPCRs) with indirect influence on the effects of an orthosteric ligand. Such modulators exhibit significant advantages compared to the corresponding orthosteric ligands, including better chemical tractability or physicochemical properties, improved selectivity, and reduced risk of oversensitization towards their receptors. Metabotropic glutamate receptor 5 (mGlu5), a member of class C GPCRs, is a promising therapeutic target for treating many central nervous system diseases...
May 30, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28554312/calcium-signaling-pkc-gamma-ip3r1-and-car8-link-spinocerebellar-ataxias-and-purkinje-cell-dendritic-development
#18
Etsuko Shimobayashi, Josef P Kapfhammer
Spinocerebellar ataxias (SCAs) are a group of cerebellar diseases characterized by progressive ataxia and cerebellar atrophy. The common symptoms of the SCAs result from damage to the cerebellum and/or its neuronal connections and share some clinical and neuropathological features such as Purkinje cell degeneration. The most common forms of SCAs are caused by expansion of CAG repeats similar to other polyglutamine disorders like Huntington's disease while several other forms of SCAs are caused by missense mutations or deletions in genes related to calcium signaling in Purkinje cells...
May 28, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28554247/association-of-social-defeat-stress-induced-anhedonia-like-symptoms-with-mglur1-dependent-downregulation-of-membrane-ampa-glur1-in-the-mouse-ventral-midbrain
#19
Sayori Yashiro, Kenjiro Seki
Anhedonia is a core symptom of social defeat stress (SDS)-induced depression associated with the reward system. We previously reported that membrane AMPA-GluR1 downregulation in the reward system is associated with lipopolysaccharide-induced anhedonia-like symptoms. Since group I metabotropic glutamate receptor (mGluR) activation reduces the surface density of GluR1, we examined whether group I mGluR-dependent membrane GluR1 downregulation in the reward system is involved in SDS-induced anhedonia-like symptoms...
May 29, 2017: Stress: the International Journal on the Biology of Stress
https://www.readbyqxmd.com/read/28553558/phosphorylation-of-group-i-metabotropic-glutamate-receptors-in-drug-addiction-and-translational-research
#20
Li-Min Mao, Qiang Wang
Protein phosphorylation is an important posttranslational modification of group I metabotropic glutamate receptors (mGluR1 and mGluR5 subtypes) which are widely distributed throughout the mammalian brain. Several common protein kinases are involved in this type of modification, including protein kinase A, protein kinase C, and extracellular signal-regulated kinase. Through constitutive and activity-dependent phosphorylation of mGluR1/5 at specific residues, protein kinases regulate trafficking, subcellular/subsynaptic distribution, and function of modified receptors...
September 2016: J Transl Neurosci
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