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Metabotropic glutamate receptor

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https://www.readbyqxmd.com/read/28320199/comparison-of-imaging-using-11-c-itmm-and-18-f-fdg-for-the-detection-of-cerebellar-ataxia
#1
Kenji Ishibashi, Yoshiharu Miura, Jun Toyohara, Kenji Ishii, Kiichi Ishiwata
Objective Newly developed methods for imaging type 1 metabotropic glutamate receptor (mGluR1) have the potential use for estimating cerebellar function. We aimed to compare mGluR1 imaging using N-[4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-4-(11)C-methoxy-N-methylbenzamide ((11)C-ITMM) with the existing marker, fluorine-18-labeled fluorodeoxyglucose ((18)F-FDG) imaging, in the cerebellum. METHODS: Fourteen subjects consisting of 12 patients with cerebellar ataxia and two healthy subjects underwent (11)C-ITMM and (18)F-FDG positron emission tomography...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28318542/monoamine-transporters-as-ionotropic-receptors
#2
Louis J De Felice
It is well established that glutamate and GABA signal through both ionotropic and metabotropic receptors. Conversely, it is thought that, with one exception, monoamines (dopamine, serotonin, and norepinephrine) signal via metabotropic receptors. Given their capacity to generate fast-acting currents, I suggest that the monoamine transporters should be considered as ionotropic receptors.
March 16, 2017: Trends in Neurosciences
https://www.readbyqxmd.com/read/28306571/cns-syndromes-associated-with-antibodies-against-metabotropic-receptors
#3
Eric Lancaster
PURPOSE OF REVIEW: Autoantibodies to Central nervous system (CNS) metabotropic receptors are associated with a growing family of autoimmune brain diseases, including encephalitis, basal ganglia encephalitis, Ophelia syndrome, and cerebellitis. The purpose of this review is to summarize the state of knowledge regarding the target receptors, the neurological autoimmune disorders, and the pathogenic mechanisms. RECENT FINDINGS: Antibodies to the γ-aminobutyric acid B receptor are associate with limbic encephalitis and severe seizures, often with small cell lung cancers...
March 16, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28300633/the-medullary-dorsal-reticular-nucleus-as-a-relay-for-descending-pronociception-induced-by-the-mglur5-in-the-rat-infralimbic-cortex
#4
Ana David-Pereira, Boriss Sagalajev, Hong Wei, Armando Almeida, Antti Pertovaara, Filipa Pinto-Ribeiro
Metabotropic glutamate receptor 5 (mGluR5) activation in the infralimbic cortex (IL) induces pronociceptive behavior in healthy and monoarthritic rats. Here we studied whether the medullary dorsal reticular nucleus (DRt) and the spinal TRPV1 are mediating the IL/mGluR5-induced spinal pronociception and whether the facilitation of pain behavior is correlated with changes in spinal dorsal horn neuron activity. For drug administrations, all animals had a cannula in the IL as well as a cannula in the DRt or an intrathecal catheter...
March 11, 2017: Neuroscience
https://www.readbyqxmd.com/read/28295323/crip1a-inhibits-endocytosis-of-g-protein-coupled-receptors-activated-by-endocannabinoids-and-glutamate-by-a-common-molecular-mechanism
#5
Fabrizio Mascia, Lisa Klotz, Judith Lerch, Mostafa A Ahmed, Yan Zhang, Ralf Enz
The excitability of the central nervous system depends largely on the surface density of neurotransmitter receptors. The endocannabinoid receptor CB1 R and the metabotropic glutamate receptor mGlu8 R are expressed presynaptically where they reduce glutamate release into the synaptic cleft. Recently, the CB1 R interacting protein CRIP1a was identified and characterized to regulate CB1 R activity in neurons. However, underlying molecular mechanisms are largely unknown. Here, we identified a common mechanism used by CRIP1a to regulate the cell surface density of two different types of G-protein coupled receptors, CB1 R and mGlu8a R...
March 15, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28286129/fret-based-sensors-unravel-activation-and-allosteric-modulation-of-the-gabab-receptor
#6
Nathalie Lecat-Guillet, Carine Monnier, Xavier Rovira, Julie Kniazeff, Laurent Lamarque, Jurriaan M Zwier, Eric Trinquet, Jean-Philippe Pin, Philippe Rondard
The main inhibitory neurotransmitter, γ-aminobutyric acid (GABA), modulates many synapses by activating the G protein-coupled receptor GABAB, which is a target for various therapeutic applications. It is an obligatory heterodimer made of GB1 and GB2 that can be regulated by positive allosteric modulators (PAMs). The molecular mechanism of activation of the GABAB receptor remains poorly understood. Here, we have developed FRET-based conformational GABAB sensors compatible with high-throughput screening. We identified conformational changes occurring within the extracellular and transmembrane domains upon receptor activation, which are smaller than those observed in the related metabotropic glutamate receptors...
March 16, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28285415/naag-peptidase-inhibitors-act-via-mglur3-animal-models-of-memory-alzheimer-s-and-ethanol-intoxication
#7
Rafal T Olszewski, Karolina J Janczura, Tomasz Bzdega, Elise K Der, Faustino Venzor, Brennen O'Rourke, Timothy J Hark, Kirsten E Craddock, Shankar Balasubramanian, Charbel Moussa, Joseph H Neale
Glutamate carboxypeptidase II (GCPII) inactivates the peptide neurotransmitter N-acetylaspartylglutamate (NAAG) following synaptic release. Inhibitors of GCPII increase extracellular NAAG levels and are efficacious in animal models of clinical disorders via NAAG activation of a group II metabotropic glutamate receptor. mGluR2 and mGluR3 knock-out (ko) mice were used to test the hypothesis that mGluR3 mediates the activity of GCPII inhibitors ZJ43 and 2-PMPA in animal models of memory and memory loss. Short- (1...
March 11, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28282540/ionotropic-ampa-type-glutamate-and-metabotropic-gabab-receptors-determining-cellular-physiology-by-proteomes
#8
REVIEW
Bernhard Bettler, Bernd Fakler
Ionotropic AMPA-type glutamate receptors and G-protein-coupled metabotropic GABAB receptors are key elements of neurotransmission whose cellular functions are determined by their protein constituents. Over the past couple of years unbiased proteomic approaches identified comprehensive sets of protein building blocks of these two types of neurotransmitter receptors in the brain (termed receptor proteomes). This provided the opportunity to match receptor proteomes with receptor physiology and to study the structural organization, regulation and function of native receptor complexes in an unprecedented manner...
March 7, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/28275711/the-kinase-function-of-msk1-regulates-bdnf-signaling-to-creb-and-basal-synaptic-transmission-but-is-not-required-for-hippocampal-long-term-potentiation-or-spatial-memory
#9
Stephanie Daumas, Christopher J Hunter, Rajen B Mistry, Lorenzo Morè, Lucia Privitera, Daniel D Cooper, Kathleen M Reyskens, Harry T Flynn, Richard G M Morris, J Simon C Arthur, Bruno G Frenguelli
The later stages of long-term potentiation (LTP) in vitro and spatial memory in vivo are believed to depend upon gene transcription. Accordingly, considerable attempts have been made to identify both the mechanisms by which transcription is regulated and indeed the gene products themselves. Previous studies have shown that deletion of one regulator of transcription, the mitogen- and stress-activated kinase 1 (MSK1), causes an impairment of spatial memory. Given the ability of MSK1 to regulate gene expression via the phosphorylation of cAMP response element binding protein (CREB) at serine 133 (S133), MSK1 is a plausible candidate as a prime regulator of transcription underpinning synaptic plasticity and learning and memory...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28273557/curcumin-inhibiting-th17-cell-differentiation-by-regulating-the-metabotropic-glutamate-receptor-4-expression-on-dendritic-cells
#10
Guangming Zhao, Ying Liu, Xiaying Yi, Yupeng Wang, Song Qiao, Zhen Li, Jing Ni, Zhiqi Song
Th17 cells have been categorized as a new lineage of CD4+ T cells, and played a crucial role in the pathogenesis of numerous autoimmune disorders. Type 4 metabotropic glutamate receptor (mGluR4), a member of group III mGluRs, recently has been found to be expressed in many types of immune cells and mediate adaptive immunity. Curcumin has been shown to exhibit potent anti-inflammatory, antimutagenic and anticarcinogenic properties. For the past few years, it has gradually been regarded as an pluripotent immunomodulatory agent that can regulate the activation of immune cells...
March 4, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28267198/serotonergic-transmission-at-merkel-discs-modulation-by-exogenously-applied-chemical-messengers-and-involvement-of-ih-currents
#11
Weipang Chang, Hirosato Kanda, Ryo Ikeda, Jennifer Ling, Jianguo G Gu
The Merkel disc is a main type of tactile end organ consisting of Merkel cells and Aβ-afferent endings that responds to tactile stimulation with slowly adapting type 1 (SA1) afferent impulses. Our recent study has shown that Merkel discs in whisker hair follicles are serotonergic synapses using endogenous serotonin to transmit tactile signals from Merkel cells to Aβ-afferent endings. In the present study, we hypothesize that tactile sensitivity of Merkel discs can be modulated by chemical messengers. We tested this hypothesis by determining whether and how SA1 responses of mouse whisker hair follicles may be affected by exogenously applied chemical messengers...
March 7, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28266711/pkc-epsilon-dependent-calcium-oscillations-associated-with-metabotropic-glutamate-receptor-5-prevent-agonist-mediated-receptor-desensitization-in-astrocytes
#12
Maxime Vergouts, Pierre J Doyen, Michael Peeters, Remi Opsomer, Thomas Michiels, Emmanuel Hermans
A critical role has been assigned to PKCε in the control of intracellular calcium oscillations triggered upon activation of type 5 metabotropic glutamate receptor (mGluR5) in cultured astrocytes. Nevertheless, the physiological significance of this particular signalling profile in the response of astrocytes to glutamate remains largely unknown. Considering that kinases are frequently involved in the regulation of G-protein coupled receptors, we have examined a putative link between the nature of the calcium signals and the response regulation upon repeated exposures of astrocytes to the agonist (S)-3,5-dihydroxyphenylglycine...
March 7, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28265857/differences-in-5-ht2a-and-mglu2-receptor-expression-levels-and-repressive-epigenetic-modifications-at-the-5-ht2a-promoter-region-in-the-roman-low-rla-i-and-high-rha-i-avoidance-rat-strains
#13
Luna Fomsgaard, Jose L Moreno, Mario de la Fuente Revenga, Tomasz Brudek, Dea Adamsen, Cristobal Rio-Alamos, Justin Saunders, Anders Bue Klein, Ignasi Oliveras, Toni Cañete, Gloria Blazquez, Adolf Tobeña, Albert Fernandez-Teruel, Javier Gonzalez-Maeso, Susana Aznar
The serotonin 2A (5-HT2A) and metabotropic glutamate 2 (mGlu2) receptors regulate each other and are associated with schizophrenia. The Roman high- (RHA-I) and the Roman low- (RLA-I) avoidance rat strains present well-differentiated behavioral profiles, with the RHA-I strain emerging as a putative genetic rat model of schizophrenia-related features. The RHA-I strain shows increased 5-HT2A and decreased mGlu2 receptor binding levels in prefrontal cortex (PFC). Here, we looked for differences in gene expression and transcriptional regulation of these receptors...
March 6, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28263042/1-3-5-trisubstituted-pyrazoles-as-potent-negative-allosteric-modulators-of-the-mglu2-3-receptors
#14
Michiel Van Gool, Sergio Alvar Alonso De Diego, Oscar Delgado, Andrés A Trabanco, Fabrice Jourdan, Gregor J Macdonald, Marijke Somers, Luc Ver Donck
The metabotropic glutamate subtype 2 (mGlu2) receptor is a presynaptic membrane receptor distributed widely in brain that provides feedback inhibitory control of glutamate release. Inhibition of the mGlu2 receptor function with a negative allosteric modulator (NAM) enhances activity dependent glutamate release which may be of therapeutic benefit for treatment of neurological and psychiatric disorders. An attractive pyrazole hit was identified after a high throughput screening (HTS) campaign. The evolution of this hit is described by structure-activity relationship (SAR) study on specific parts of the molecule...
March 6, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28262417/cell-autonomous-excitation-of-midbrain-dopamine-neurons-by-endocannabinoid-dependent-lipid-signaling
#15
Stephanie C Gantz, Bruce P Bean
The major endocannabinoid in the mammalian brain is the bioactive lipid 2-arachidonoylglycerol (2-AG). The best-known effects of 2-AG are mediated by G-protein-coupled cannabinoid receptors. In principle, 2-AG could modify neuronal excitability by acting directly on ion channels, but such mechanisms are poorly understood. Using a preparation of dissociated mouse midbrain dopamine neurons to isolate effects on intrinsic excitability, we found that 100 nM 2-AG accelerated pacemaking and steepened the frequency-current relationship for burst-like firing...
February 21, 2017: Neuron
https://www.readbyqxmd.com/read/28262416/the-auxiliary-calcium-channel-subunit-%C3%AE-2%C3%AE-4-is-required-for-axonal-elaboration-synaptic-transmission-and-wiring-of-rod-photoreceptors
#16
Yuchen Wang, Katherine E Fehlhaber, Ignacio Sarria, Yan Cao, Norianne T Ingram, Debbie Guerrero-Given, Ben Throesch, Kristin Baldwin, Naomi Kamasawa, Toshihisa Ohtsuka, Alapakkam P Sampath, Kirill A Martemyanov
Neural circuit wiring relies on selective synapse formation whereby a presynaptic release apparatus is matched with its cognate postsynaptic machinery. At metabotropic synapses, the molecular mechanisms underlying this process are poorly understood. In the mammalian retina, rod photoreceptors form selective contacts with rod ON-bipolar cells by aligning the presynaptic voltage-gated Ca(2+) channel directing glutamate release (CaV1.4) with postsynaptic mGluR6 receptors. We show this coordination requires an extracellular protein, α2δ4, which complexes with CaV1...
February 23, 2017: Neuron
https://www.readbyqxmd.com/read/28251297/glutamate-carboxypeptidase-ii-gcpii-inhibitor-2-pmpa-reduces-rewarding-effects-of-the-synthetic-cathinone-mdpv-in-rats-a-role-for-n-acetylaspartylglutamate-naag
#17
Callum Hicks, Ryan A Gregg, Sunil U Nayak, Lee Anne Cannella, Giana J Schena, Christopher S Tallarida, Allen B Reitz, Garry R Smith, Scott M Rawls
RATIONALE: Metabotropic glutamate 2 and 3 (mGluR2/3) receptors are implicated in drug addiction as they limit excessive glutamate release during relapse. N-acetylaspartylglutamate (NAAG) is an endogenous mGluR2/3 agonist that is inactivated by the glutamate carboxypeptidase II (GCPII) enzyme. GCPII inhibitors, and NAAG itself, attenuate cocaine-seeking behaviors. However, their effects on the synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV) have not been examined. OBJECTIVES: We determined whether withdrawal following repeated MDPV administration alters GCPII expression in corticolimbic regions...
March 1, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28242339/metabotropic-and-ionotropic-glutamate-receptors-as-potential-targets-for-the-treatment-of-alcohol-use-disorder
#18
REVIEW
Sunil Goodwani, Hannah Saternos, Fawaz Alasmari, Youssef Sari
Emerging evidence indicates that dysfunctional glutamate neurotransmission is critical in the initiation and development of alcohol and drug dependence. Alcohol consumption induced downregulation of glutamate transporter 1 (GLT-1) as reported in previous studies from our laboratory. Glutamate is the major excitatory neurotransmitter in the brain, which acts via interactions with several glutamate receptors. Alcohol consumption interferes with the glutamatergic signal transmission by altering the functions of these receptors...
February 24, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28237619/glutamate-affects-the-production-of-epoxyeicosanoids-within-the-brain-the-up-regulation-of-brain-cyp2j-through-the-mapk-creb-signaling-pathway
#19
Mingzhou Liu, Quanfei Zhu, Jinhua Wu, Xuming Yu, Mingbai Hu, Xianfei Xie, Zheqiong Yang, Jing Yang, Yu-Qi Feng, Jiang Yue
Glutamate is the major excitatory neurotransmitter in the brain, and chronic glutamate excitotoxicity has been thought to be involved in numerous neurodegenerative diseases. We investigated the effects of glutamate at concentrations lower than the usual extrasynaptic concentrations on the production of epoxyeicosanoids mediated by brain CYP2J. Glutamate increased CYP2J2 mRNA levels in astrocytes in a dose-dependent manner, while an antagonist of the metabotropic glutamate receptor subtype 5 (mGlu5 receptor) attenuated the glutamate-induced increases in CYP2J2 levels by glutamate...
April 15, 2017: Toxicology
https://www.readbyqxmd.com/read/28236206/glutamate-t-cells-and-multiple-sclerosis
#20
REVIEW
Mia Levite
Glutamate is the major excitatory neurotransmitter in the nervous system, where it induces multiple beneficial and essential effects. Yet, excess glutamate, evident in a kaleidoscope of acute and chronic pathologies, is absolutely catastrophic, since it induces excitotoxicity and massive loss of brain function. Both the beneficial and the detrimental effects of glutamate are mediated by a large family of glutamate receptors (GluRs): the ionotropic glutamate receptors (iGluRs) and the metabotropic glutamate receptors (mGluRs), expressed by most/all cells of the nervous system, and also by many non-neural cells in various peripheral organs and tissues...
February 24, 2017: Journal of Neural Transmission
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