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Metabotropic glutamate receptor

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https://www.readbyqxmd.com/read/27920147/accumbens-nnos-interneurons-regulate-cocaine-relapse
#1
Alexander C W Smith, Michael D Scofield, Jasper A Heinsbroek, Cassandra D Gipson, Daniela Neuhofer, Doug J Roberts-Wolfe, Sade Spencer, Neringa M Stankeviciute, Rachel Smith, Nicholas P Allen, Melissa R Lorang, William C Griffin, Heather A Boger, Peter W Kalivas
: Relapse to drug use can be initiated by drug-associated cues. The intensity of cue-induced relapse is correlated with the induction of transient synaptic potentiation (t-SP) at glutamatergic synapses on medium spiny neurons (MSNs) in the nucleus accumbens core (NAcore), and requires spillover of glutamate from prefrontal cortical afferents. We used a rodent self-administration/reinstatement model of relapse to show that cue-induced t-SP and reinstated cocaine-seeking result from glutamate spillover initiating a metabotropic glutamate receptor 5 (mGluR5)-dependent increase in nitric oxide (NO) production...
December 5, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27916557/histone-acetylation-and-histone-deacetylation-in-neuropathic-pain-an-unresolved-puzzle
#2
REVIEW
Ravneet Kaur Khangura, Anjana Bali, Amteshwar Singh Jaggi, Nirmal Singh
Chronic pain is broadly classified into somatic, visceral or neuropathic pain depending upon the location and extent of pain perception. Evidences from different animal studies suggest that inflammatory or neuropathic pain is associated with altered acetylation and deacetylation of histone proteins, which result in abnormal transcription of nociceptive processing genes. There have been a number of studies indicating that nerve injury up-regulates histone deacetylase enzymes, which leads to increased histone deacetylation and induce chronic pain...
December 2, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27914294/selective-agonism-of-mglu8-receptors-by-s-3-4-dicarboxyphenylglycine-does-not-affect-sleep-stages-in-the-rat
#3
María Cavas, Gianluigi Scesa, Mercedes Martín-López, José Francisco Navarro
BACKGROUND: Metabotropic glutamate receptors (mGlu) play a role in a number of physiological processes and behaviors, as well as in certain pathological conditions and diseases. New drugs targetting mGlu receptors are being developed with treatment purposes. Recent data indicates that glutamate is involved in sleep, and pharmacological manipulation of distinct subtypes of mGlu receptors affect sleep. Here the consequences of selective pharmacological agonism of mGlu8 receptor upon sleep and wakefulness are explored for the first time...
September 22, 2016: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/27913207/overexpression-of-stim1-in-neurons-in-mouse-brain-improves-contextual-learning-and-impairs-long-term-depression
#4
Łukasz Majewski, Filip Maciąg, Paweł M Boguszewski, Iga Wasilewska, Grzegorz Wiera, Tomasz Wójtowicz, Jerzy Mozrzymas, Jacek Kuznicki
STIM1 is an endoplasmic reticulum calcium sensor that is involved in several processes in neurons, including store-operated calcium entry. STIM1 also inhibits voltage-gated calcium channels, such as Cav1.2 and Cav3.1, and is thus considered a multifunctional protein. The aim of this work was to investigate the ways in which transgenic neuronal overexpression of STIM1 in FVB/NJ mice affects animal behavior and the electrophysiological properties of neurons in acute hippocampal slices. We overexpressed STIM1 from the Thy1...
November 29, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27911756/activation-of-group-ii-metabotropic-glutamate-receptors-promotes-ltp-induction-at-schaffer-collateral-ca1-pyramidal-cell-synapses-by-priming-nmda-receptors
#5
Nadia Rosenberg, Urs Gerber, Jeanne Ster
: It is well established that selective activation of group I metabotropic glutamate (mGlu) receptors induces LTD of synaptic transmission at Schaffer collateral-CA1 synapses. In contrast, application of 1S,3R-ACPD, a mixed agonist at group I and group II mGlu receptors, induces LTP. Using whole-cell recordings from CA1 pyramidal cells and field recordings in the hippocampal CA1 region, we investigated the specific contribution of group II mGlu receptors to synaptic plasticity at Schaffer collateral-CA1 synapses in acute slices of adult mice...
November 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27908790/mpp-inhibits-mglur1-5-mediated-long-term-depression-in-mouse-hippocampus-by-calpain-activation
#6
Junyao Li, Hui Chen, Shengbing Wu, Yuefa Cheng, Qinglin Li, Jing Wang, Guoqi Zhu
Neurotoxins are harmful to nervous system and cause either neuronal cell death or impairment of synaptic activity, which contributes to Parkinson's disease or other neuronal disorders. Hippocampal synaptic plasticity was proposed as a cellular model for memory processing. In this study, we reported a novel effect of neurotoxin, 1-methyl-4-phenylpyridinium (MPP(+)), on metabotropic glutamate receptor 1/5 agonist, 3,5-dihydroxyphenylglycine (DHPG)-induced hippocampal synaptic plasticity, and MPP(+) incubation blocked DHPG-induced hippocampal long-term depression (LTD) in Schaffer collateral-CA1 synapses...
November 29, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27908770/metabotropic-glutamate-receptors-5-years-on
#7
EDITORIAL
Graham Collingridge, Denise Manahan-Vaughan, Ferdinando Nicoletti, Darryle Schoepp
No abstract text is available yet for this article.
November 28, 2016: Neuropharmacology
https://www.readbyqxmd.com/read/27908761/discovery-of-dual-positive-allosteric-modulators-pams-of-the-metabotropic-glutamate-2-receptor-and-cyslt1-antagonists-for-treating-migraine-headache
#8
Maria-Jesus Blanco, Dana R Benesh, James A Knobelsdorf, Albert Khilevich, Guillermo S Cortez, Fese Mokube, Thomas D Aicher, Todd M Groendyke, Fredrik P Marmsater, Tony P Tang, Kirk W Johnson, Amy Clemens-Smith, Mark A Muhlhauser, Steven Swanson, John Catlow, Renee Emkey, Michael P Johnson, Jeffrey M Schkeryantz
Pyridylmethylsulfonamide series were the first reported example of positive allosteric modulators (PAM) of the mGlu2 receptor. The hydroxyacetophenone scaffold is a second series of mGlu2 PAMs we have identified. This series of molecules are potent mGlu2 potentiators and possess significant CysLT1 (cysteinyl leukotriene receptor 1) antagonist activity, showing in vivo efficacy in a dural plasma protein extravasation (PPE) model of migraine. In this paper, we describe the dual SAR, pharmacokinetics and preclinical in vivo efficacy data for a tetrazole containing hydroxyacetophenone scaffold...
November 18, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27905440/organization-and-functions-of-mglu-and-gabab-receptor-complexes
#9
Jean-Philippe Pin, Bernhard Bettler
The neurotransmitters glutamate and γ-aminobutyric acid (GABA) transmit synaptic signals by activating fast-acting ligand-gated ion channels and more slowly acting G-protein-coupled receptors (GPCRs). The GPCRs for these neurotransmitters, metabotropic glutamate (mGlu) and GABAB receptors, are atypical GPCRs with a large extracellular domain and a mandatory dimeric structure. Recent studies have revealed how these receptors are activated through multiple allosteric interactions between subunit domains. It emerges that the molecular complexity of these receptors is further increased through association with trafficking, effector and regulatory proteins...
December 1, 2016: Nature
https://www.readbyqxmd.com/read/27895114/in-vitro-and-clinical-evaluations-of-the-drug-drug-interaction-potential-of-a-metabotropic-glutamate-2-3-receptor-agonist-prodrug-at-pept1
#10
Y Anne Pak, Amanda J Long, William F Annes, Jennifer W Witcher, Mary Pat Knadler, Mosun A Ayan-Oshodi, Malcolm I Mitchell, Phillip Leese, Kathleen M Hillgren
Despite PEPT1 being responsible for the bioavailability for a variety of drugs, there has been little study of its potential involvement in drug-drug interactions. Pomaglumetad methionil, a metabotropic glutamate 2/3 receptor agonist prodrug, utilizes PEPT1 to enhance absorption and bioavailability. In vitro studies were conducted to guide the decision to conduct a clinical drug interaction study and to inform the clinical study design. In vitro investigations determined the prodrug (LY2140023 monohydrate) is a substrate of PEPT1 with Km value of approximately 30 μM, while the active moiety (LY404039) is not a PEPT1 substrate...
November 28, 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/27891197/the-oscillation-like-activity-in-bullfrog-on-off-retinal-ganglion-cell
#11
Xiao-Wei Qiu, Hai-Qing Gong, Pu-Ming Zhang, Pei-Ji Liang
Oscillatory activity of retinal ganglion cell (RGC) has been observed in various species. It was reported such oscillatory activity is raised within large neural network and involved in retinal information coding. In the present research, we found an oscillation-like activity in ON-OFF RGC of bullfrog retina, and studied the mechanisms underlying the ON and OFF activities respectively. Pharmacological experiments revealed that the oscillation-like activity patterns in both ON and OFF pathways were abolished by GABA receptor antagonists, indicating GABAergic inhibition is essential for generating them...
December 2016: Cognitive Neurodynamics
https://www.readbyqxmd.com/read/27891077/presynaptic-g-protein-coupled-receptors-gatekeepers-of-addiction
#12
REVIEW
Kari A Johnson, David M Lovinger
Drug abuse and addiction cause widespread social and public health problems, and the neurobiology underlying drug actions and drug use and abuse is an area of intensive research. Drugs of abuse alter synaptic transmission, and these actions contribute to acute intoxication as well as the chronic effects of abused substances. Transmission at most mammalian synapses involves neurotransmitter activation of two receptor subtypes, ligand-gated ion channels that mediate fast synaptic responses and G protein-coupled receptors (GPCRs) that have slower neuromodulatory actions...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27890550/paradoxical-sleep-deprivation-in-rats-causes-a-selective-reduction-in-the-expression-of-type-2-metabotropic-glutamate-receptors-in-the-hippocampus
#13
Isabella Panaccione, Luisa Iacovelli, Luigi di Nuzzo, Francesca Nardecchia, Gianluca Mauro, Delfina Janiri, Antonio De Blasi, Gabriele Sani, Ferdinando Nicoletti, Rosamaria Orlando
Paradoxical sleep deprivation in rats is considered as an experimental animal model of mania endowed with face, construct, and pharmacological validity. We induced paradoxical sleep deprivation by placing rats onto a small platform surrounded by water. This procedure caused the animal to fall in the water at the onset of REM phase of sleep. Control rats were either placed onto a larger platform (which allowed them to sleep) or maintained in their home cage. Sleep deprived rats showed a substantial reduction in type-2 metabotropic glutamate (mGlu2) receptors mRNA and protein levels in the hippocampus, but not in the prefrontal cortex or corpus striatum, as compared to both groups of control rats...
November 23, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27890469/methamphetamine-addiction-vulnerability-the-glutamate-the-bad-and-the-ugly
#14
Karen K Szumlinski, Kevin D Lominac, Rianne R Campbell, Matan Cohen, Elissa K Fultz, Chelsea N Brown, Bailey W Miller, Sema G Quadir, Douglas Martin, Andrew B Thompson, Georg von Jonquieres, Matthias Klugmann, Tamara J Phillips, Tod E Kippin
BACKGROUND: The high prevalence and severity of methamphetamine (MA) abuse demands greater neurobiological understanding of its etiology. METHODS: We conducted immunoblotting and in vivo microdialysis procedures in MA high/low drinking mice, as well as in isogenic C57BL/6J mice that varied in their MA preference/taking, to examine the glutamate underpinnings of MA abuse vulnerability. Neuropharmacological and Homer2 knockdown approaches were also used in C57BL/6J mice to confirm the role for nucleus accumbens (NAC) glutamate/Homer2 expression in MA preference/aversion...
October 13, 2016: Biological Psychiatry
https://www.readbyqxmd.com/read/27886179/astrocytic-gaba-transporter-activity-modulates-excitatory-neurotransmission
#15
Kim Boddum, Thomas P Jensen, Vincent Magloire, Uffe Kristiansen, Dmitri A Rusakov, Ivan Pavlov, Matthew C Walker
Astrocytes are ideally placed to detect and respond to network activity. They express ionotropic and metabotropic receptors, and can release gliotransmitters. Astrocytes also express transporters that regulate the extracellular concentration of neurotransmitters. Here we report a previously unrecognized role for the astrocytic GABA transporter, GAT-3. GAT-3 activity results in a rise in astrocytic Na(+) concentrations and a consequent increase in astrocytic Ca(2+) through Na(+)/Ca(2+) exchange. This leads to the release of ATP/adenosine by astrocytes, which then diffusely inhibits neuronal glutamate release via activation of presynaptic adenosine receptors...
November 25, 2016: Nature Communications
https://www.readbyqxmd.com/read/27886171/transduction-of-group-i-mglur-mediated-synaptic-plasticity-by-%C3%AE-arrestin2-signalling
#16
Andrew G Eng, Daniel A Kelver, Tristan P Hedrick, Geoffrey T Swanson
Conventional signalling by the group I metabotropic glutamate receptors, mGluR1 and mGluR5, occurs through G-protein coupling, but evidence suggests they might also utilize other, non-canonical effector pathways. Here we test whether group I mGluRs require β-arrestin signalling during specific forms of plasticity at hippocampal excitatory synapses. We find that genetic ablation of β-arrestin2, but not β-arrestin1, results in deficits in plasticity mediated by mGlu1 receptors in CA3 pyramidal neurons and by mGlu5 receptors in CA1 pyramidal neurons...
November 25, 2016: Nature Communications
https://www.readbyqxmd.com/read/27881780/negative-allosteric-modulation-of-mglur5-partially-corrects-pathophysiology-in-a-mouse-model-of-rett-syndrome
#17
Jifang Tao, Hao Wu, Amanda A Coronado, Elizabeth de Laittre, Emily K Osterweil, Yi Zhang, Mark F Bear
: Rett syndrome (RTT) is caused by mutations in the gene encoding methyl-CpG binding protein 2 (MECP2), an epigenetic regulator of mRNA transcription. Here, we report a test of the hypothesis of shared pathophysiology of RTT and fragile X, another monogenic cause of autism and intellectual disability. In fragile X, the loss of the mRNA translational repressor FMRP leads to exaggerated protein synthesis downstream of metabotropic glutamate receptor 5 (mGluR5). We found that mGluR5- and protein-synthesis-dependent synaptic plasticity were similarly altered in area CA1 of Mecp2 KO mice...
November 23, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27880915/blunted-mglur-activation-disinhibits-striatopallidal-transmission-in-parkinsonian-mice
#18
Qiaoling Cui, Jason E Pitt, Arin Pamukcu, Jean-Francois Poulin, Omar S Mabrouk, Michael P Fiske, Isabel B Fan, Elizabeth C Augustine, Katherine A Young, Robert T Kennedy, Rajeshwar Awatramani, C Savio Chan
The prevailing circuit model predicts that hyperactivity of the striatopallidal pathway and subsequently increased inhibition of external globus pallidus (GPe) neurons lead to the hypokinetic symptoms of Parkinson's disease (PD). It is believed that hyperactivity of the striatopallidal pathway is due to inactivity of dopamine receptors on the somatodendritic membrane of striatopallidal neurons, but the exact cellular underpinnings remain unclear. In this study, we show that mouse GPe astrocytes critically control ambient glutamate level, which in turn gates striatopallidal transmission via the activation of presynaptic metabotropic glutamate receptors...
November 22, 2016: Cell Reports
https://www.readbyqxmd.com/read/27872582/separate-ionotropic-and-metabotropic-glutamate-receptor-functions-in-depotentiation-vs-ltp-a-distinct-role-for-group1-mglur-subtypes-and-nmdars
#19
Amira Latif-Hernandez, Enrico Faldini, Tariq Ahmed, Detlef Balschun
Depotentiation (DP) is a mechanism by which synapses that have recently undergone long-term potentiation (LTP) can reverse their synaptic strengthening within a short time-window after LTP induction. Group 1 metabotropic glutamate receptors (mGluRs) were shown to be involved in different forms of LTP and long-term depression (LTD), but little is known about their roles in DP. Here, we generated DP by applying low-frequency stimulation (LFS) at 5 Hz after LTP had been induced by a single train of theta-burst-stimulation (TBS)...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27872019/metabotropic-glutamate-receptors-and-neurodegenerative-diseases
#20
REVIEW
Fabiola M Ribeiro, Luciene B Vieira, Rita G W Pires, Roenick P Olmo, Stephen S G Ferguson
Glutamate is the most important excitatory neurotransmitter of the mammalian central nervous system (CNS), playing an important role in memory, synaptic plasticity and neuronal development. However, glutamate overstimulation is also implicated in neuronal cell death. There are two major types of glutamate receptors: ionotropic and metabotropic. Thus far, eight metabotropic glutamate receptors (mGluRs) subtypes have been characterized and are divided into three subgroups based on sequence homology and cell signaling activation...
November 19, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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