TY - JOUR. T1 - Molecular characterization of a novel metabotropic glutamate receptor mGluR5 coupled to inositol phosphate/Ca2+ signal transduction. AU - Abe, T.. AU - Sugihara, H.. AU - Nawa, H.. AU - Shigemoto, R.. AU - Mizuno, N.. AU - Nakanishi, S.. N1 - Copyright: Copyright 2004 Elsevier B.V., All rights reserved.. PY - 1992. Y1 - 1992. N2 - A cDNA clone for a new metabotropic glutamate receptor, mGluR5, was isolated through polymerase chain reaction-mediated DNA amplification by using primer sequences conserved among the metabotropic glutamate receptor (mGluR) family and by the subsequent screening of a rat brain cDNA library. The cloned receptor consists of 1171 amino acid residues and exhibits a structural architecture common to the mGluR family, possessing a large extracellular domain preceding the seven putative membrane-spanning segments. mGluR5 shows the highest sequence similarity to mGluR1 among the mGluR members and is coupled to the stimulation of phosphatidylinositol ...

Title: Targeting the Metabotropic Glutamate Receptor mGluR4 for the Treatment of Diseases of the Central Nervous System. VOLUME: 5 ISSUE: 9. Author(s):Michael J. Marino, J. F. Hess and Nigel Liverton. Affiliation:Neuroscience Drug Discovery - Movement Disorders Research, Merck Research Laboratories, Merck&Co., PO Box 4, West Point, PA 19486, USA.. Keywords:mglur, glutamate, parkinsons disease. Abstract: Over the last several years a great deal of interest has been focused on the metabotropic glutamate receptors as potential targets for the treatment of a variety of disorders of the central nervous system. Recently, selective agonist or allosteric potentiators of mGluR4, one of the group III mGluRs, have been proposed as potential novel therapeutics for the palliative treatment of Parkinsons disease and some forms of epilepsy. mGluR4 stands out amongst the group III mGluRs due to its relatively restricted localization and apparent role in several key neuronal circuits. Work from a number of ...

TY - JOUR. T1 - Homer 1b regulates the trafficking of group I metabotropic glutamate receptors. AU - Roche, Katherine W.. AU - Tu, Jian Cheng. AU - Petralia, Ronald S.. AU - Xiao, Bo. AU - Wenthold, Robert J.. AU - Worley, Paul F. PY - 1999/9/3. Y1 - 1999/9/3. N2 - The molecular basis for glutamate receptor trafficking to the plasma membrane is not understood. In the present study, we demonstrate that Homer 1b (H1b), a constitutively expressed splice form of the immediate early gene product Homer (now termed Homer 1a) regulates the trafficking and surface expression of group I metabotropic glutamate receptors. H1b inhibits surface expression of the metabotropic glutamate receptor mGluR5 in heterologous cells, causing mGluR5 to be retained in the endoplasmic reticulum (ER). In contrast, mGluR5 alone or mGluR5 coexpressed with Homer 1a successfully travels through the secretory pathway to the plasma membrane. In addition, point mutations that disrupt mGluR5 binding to H1b eliminate ER retention of ...

TY - JOUR. T1 - Bidirectional shift of group III metabotropic glutamate receptor-mediated synaptic depression in the epileptic hippocampus. AU - Dammann, Fabian. AU - Kirschstein, Timo. AU - Guli, Xiati. AU - Müller, Steffen. AU - Porath, Katrin. AU - Rohde, Marco. AU - Tokay, Tursonjan. AU - Köhling, Rüdiger. PY - 2018/1/1. Y1 - 2018/1/1. N2 - A common function of group III metabotropic glutamate receptors (mGluRs) located at the presynaptic site of a glutamatergic synapse is synaptic depression. Here, we studied synaptic depression mediated by group III mGluR activation at Schaffer collateral-CA1 (SC-CA1) synapses and associational-commissural-CA3 (AC-CA3) synapses by recording field excitatory postsynaptic potentials in the in vitro brain slice preparation. In order to gauge the impact of synaptic depression in chronically epileptic tissue, we compared rats after pilocarpine-induced status epilepticus (post-SE) with control animals. We observed that synaptic transmission at control AC-CA3 ...

Group II metabotropic glutamate receptors (mGluR2 and mGluR3, encoded by GRM2 and GRM3) are implicated in hippocampal function and cognition, and in the pathophysiology and treatment of schizophrenia and other psychiatric disorders. However, pharmacological and behavioral studies with group II mGluR agonists and antagonists have produced complex results. Here, we studied hippocampus-dependent memory in GRM2/3 double knockout (GRM2/3-/-) mice in an iterative sequence of experiments. We found that they were impaired on appetitively motivated spatial reference and working memory tasks, and on a spatial novelty preference task that relies on animals exploratory drive, but were unimpaired on aversively motivated spatial memory paradigms. GRM2/3-/-mice also performed normally on an appetitively motivated, non-spatial, visual discrimination task. These results likely reflect an interaction between GRM2/3 genotype and the arousal-inducing properties of the experimental paradigm. The deficit seen on appetitive

Carroll, F. (2008). Antagonists at Metabotropic Glutamate Receptor Subtype 5 Structure Activity Relationships and Therapeutic Potential for Addiction: Addiction Reviews 2008. Annals of the New York Academy of Sciences, 1141, 221-232 ...

Anticonvulsive and neuroprotective effects of (2S,1R,2R,3R)-2-(2,3-dicarboxycyclopropyl) glycine (DCG-IV), a potent agonist for Group II metabotropic glutamate receptors, were examined in vivo against the excitotoxicity of kainic acid in the rat. Intraventricular injection of kainic acid (2 nmol) …

The role of phospholipase C-coupled (group I) metabotropic glutamate receptors (mGluR1 and mGluR5) in post-traumatic neuronal injury was examined using rat in vivo and in vitro models. Traumatic injury to mixed neuronal/glial cultures induced phosphoinositide hydrolysis and caused neuronal death. Pharmacological blockade of group I receptors significantly reduced these effects in vitro and decreased neurological deficits as well as neuronal loss produced by traumatic brain injury in vivo. In contrast, activation of group I receptors by a specific agonist in vitro exacerbated post-traumatic neuronal death in a dose-dependent manner. Antisense oligodeoxynucleotide directed to mGluR1, but not to mGluR5, was neuroprotective in vitro, although each oligodeoxynucleotide reduced the respective receptor-stimulated accumulation of inositol phosphates to a similar degree. Together, these findings suggest that activation of mGluR1 contributes to post-traumatic neuronal injury and that mGluR1 antagonists may have

TY - JOUR. T1 - Homer1a-Dependent Crosstalk Between NMDA and Metabotropic Glutamate Receptors in Mouse Neurons. AU - Bertaso, Federica. AU - Roussignol, Gautier. AU - Worley, Paul. AU - Bockaert, Joël. AU - Fagni, Laurent. AU - Ango, Fabrice. N1 - Copyright: Copyright 2013 Elsevier B.V., All rights reserved.. PY - 2010. Y1 - 2010. N2 - Background: A large number of evidences suggest that group-I metabotropic glutamate receptors (mGluR1a, 1b, 1c, 5a, 5b) can modulate NMDA receptor activity. Interestingly, a physical link exists between these receptors through a Homer-Shank multi-protein scaffold that can be disrupted by the immediate early gene, Homer1a. Whether such a versatile link supports functional crosstalk between the receptors is unknown. Methodology/Principal Findings: Here we used biochemical, electrophysiological and molecular biological approaches in cultured mouse cerebellar neurons to investigate this issue. We found that Homer1a or dominant negative Shank3 mutants that disrupt the ...

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease due to motor neuron (MN) loss. The mechanisms causing selective MN death are largely unknown, thus prejudicing successful pharmacological treatments. Major causes of MN damage are effects downstream of the abnormal glutamate (Glu) neurotransmission. Group I metabotropic Glu receptors (mGluR1, mGluR5) actively contribute to the excitotoxicity in ALS and represent druggable molecular targets. We previously demonstrated that halving mGluR1 or mGluR5 expression in the widely studied SOD1G93A mouse model of ALS had a positive impact on disease onset, clinical progression and survival, as well as on cellular and biochemical parameters altered in ALS. Whereas these effects were similar in female and male mGluR1 heterozygous SOD1G93Amice, only male mGluR5 heterozygous SOD1G93A mice showed improved motor skills during disease progression. To further validate the role of Group I mGluRs in ALS, we generated in this study mGluR1 or ...

To place an order online, simply browse to the product you are interested in and click on the Add to Cart button. To complete this process, you will need to confirm the size and quantity of the products that you require. To complete an order you will need to register using our simple online registration process. We do not share your contact details with any third parties.. When you are ready to check out simply enter your PO number to complete the ordering process. Please ensure that you send us a copy of your PO by fax or email afterwards. We will then liaise with you or your purchasing department to confirm the order.. ...

Fan, Wei. Conditions for activation of group I metabotropic glutamate receptors in rat hippocampus. 2010, University of Zurich, Faculty of Science. ...

Current therapies for Parkinsons disease are able to ameliorate the symptoms in the early stages, however as the disease progresses, they become less effective and patients often develop debilitating side effects. There is currently a significant unmet need for disease modifying or neuroprotective drugs to slow the rate of disease progression and provide long-term symptomatic relief. Novel therapeutics that can provide symptomatic relief whilst attenuating the ongoing neurodegeneration are therefore sought. The targeting of metabotropic glutamate (mGlu) receptors has become a therapeutic focus in recent years. The group III mGlu receptors are the focus of this thesis as they currently hold the most therapeutic promise, with evidence suggesting activation of these receptors not only modulates aberrant neurotransmission in the basal ganglia to provide symptom relief, but also provides neuroprotective effects in the nigrostriatal system through a variety of mechanisms. Recent advances in the ...

Metabotropic glutamate receptor (mGluR)-dependent calcium ion (Ca2+) signaling in astrocytic processes regulates synaptic transmission and local blood flow essential for brain function. However, because of difficulties in imaging astrocytic processes, the subcellular spatial organization of mGluR-dependent Ca2+ signaling is not well characterized and its regulatory mechanism remains unclear. Using genetically encoded Ca2+ indicators, we showed that despite global stimulation by an mGluR agonist, astrocyte processes intrinsically exhibited a marked enrichment of Ca2+ responses. Immunocytochemistry indicated that these polarized Ca2+ responses could be attributed to increased density of surface mGluR5 on processes relative to the soma. Single-particle tracking of surface mGluR5 dynamics revealed a membrane barrier that blocked the movement of mGluR5 between the processes and the soma. Overexpression of mGluR or expression of its carboxyl terminus enabled diffusion of mGluR5 between the soma and ...

Acosta-Cabronero J, Betts MJ, Cardenas-Blanco A, Yang S, Nestor PJ (2015). In vivo MRI mapping of brain iron deposition across the adult lifespan. J.Neurosci. (in press). Betts MJ, ONeill M, Duty S (2012). Allosteric modulation of the group III mGlu receptor 4 provides functional neuroprotection in the rodent 6-OHDA model of Parkinsons disease. Br J Pharmacol. Aug;166(8):2317-30. Broadstock M, Austin P, Betts MJ, Duty S (2012). Antiparkinsonian potential of targeting group III metabotropic glutamate receptor subtypes in the rodent substantia nigra pars reticulata. Br J Pharmacol. Feb;165(4b):1034-45. Austin P, *Betts MJ, Broadstock M, ONeill M, Mitchell S, Duty S (2010). Symptomatic and neuroprotective effects following activation of nigral group III metabotropic glutamate receptors in rodent models of Parkinsons disease. Br J Pharmacol. Aug;160(7):1741-5. * Denotes co-first author. Book chapters. Düzel E, Guitart-Masip M, Maaß A, Haemmerer D, Betts M, Speck O, Weiskopf N, Kanowski M ...

Metabotropic glutamate receptors (mGluRs) are G protein-coupled receptors (GPCRs) that contribute to the regulation of integrative brain functions such as cognition, motor control, and neural development. Metabotropic glutamate receptors are members of a unique class of GPCRs (class III) that include the calcium sensing and γ-aminobutyric acid type B receptors. Although mGluRs bear little sequence homology to well-characterized members of the GPCR superfamily, both second messenger-dependent protein kinases and G protein-coupled receptor kinases (GRKs) contribute to mGluR desensitization. Therefore, in the present study, we examined whether β-arrestins, regulators of GPCR desensitization and endocytosis, are required for mGluR1a desensitization and internalization in human embryonic kidney (HEK) 293 cells. Unlike what has been reported for other GPCRs, we find that in response to agonist stimulation, mGluR1a internalization is selectively mediated by β-arrestin1 in HEK 293 cells. However, ...

The mGlu5 receptor is the only metabotropic glutamate receptor subtype expressed by mouse embryonic stem (ES) cells grown under non-differentiating conditions [Cappuccio, L, Spinanti, P. Porcellini, A., Desiderati, F., De Vita, T., Storto, M., Capobianco, L., Battaglia, G., Nicoletti, F., Melchiorri, D., 2005. Endogenous activation of mGlu5 metabotropic glutamate receptors supports self-renewal of cultured mouse embryonic stem cells. Neuropharmacology 1, 196-205]. We now report that ES cells differentiating into embryoid bodies (EBs) progressively lose mGlu5 receptors and begin to express mGlu4 receptors at both mRNA and proteinc level. A 4-day treatment of EBs with the mGlu4 receptor agonist, L-2-amino-4-phosphonobutanoate (L-AP4), increased mRNA levels of the mesoderm marker, brachyury and the endoderm marker, H19, and decreased the expression of the transcript for the primitive ectoderm marker, fibroblast-growth factor-5 (FGF-5). These effects were prevented by the mGlu4 receptor antagonists, ...

Metabotropic glutamate receptors (mGluRs) play key roles in the modulation of many synapses. Chloride (Cl(-)) is known to directly bind and regulate the function of different actors of neuronal activity, and several studies have pointed to the possible modulation of mGluRs by Cl(-). Herein, we demonstrate that Cl(-) behaves as a positive allosteric modulator of mGluRs. For example, whereas glutamate potency was 3.08 ± 0.33 μM on metabotropic glutamate (mGlu) 4 receptors in high-Cl(-) buffer, signaling activity was almost abolished in low Cl(-) in cell-based assays. Cl(-) potency was 78.6 ± 3.5 mM. Cl(-) possesses a high positive cooperativity with glutamate (Hill slope ≈6 on mGlu4), meaning that small variations in [Cl(-)] lead to large variations in glutamate action. Using molecular modeling and mutagenesis, we have identified 2 well-conserved Cl(-) binding pockets in the extracellular domain of mGluRs. Moreover, modeling of activity-dependent Cl(-) variations at GABAergic synapses ...

Metabotropic glutamate receptors are G-protein coupled receptors that respond to glutamate by activating proteins inside nerve cells that affect cell metabolism, thereby fine-tuning the signals sent between cells to maintain balance in neuronal activity. Metabotropic Glutamate receptors (mGluR5) are Group I receptors localized post-synaptically and found in several regions of the brain including the striatum, hippocampus, amygdala, and cortex. Activation of mGluR5 stimulates phospholipase C, resulting in phosphoinositide hydrolysis and increase of intracellular Ca2+ levels. Several potent antagonists for mGluR5 have been developed, including 6 methyl-2-(phenylethynyl)pyridine (MPEP) and 3-[(2-methyl-1,3-thiazol-4yl)ethynyl] pyridine (MTEP) however, no simple derivatives of MPEP or MTEP had proven to be useful for in vivo imaging.. In the present protocol, we will use a new PET ligand [(18)F]SP203 for two reasons: Part 1.) we will perform kinetic brain imaging to quantify mGluR5 binding ...

Drebrin is an actin-binding protein that is preferentially expressed in the brain. It is highly localized in dendritic spines and regulates spine shapes. The embryonic-type (drebrin E) is expressed in the embryonic and early postnatal brain and is replaced by the adult-type (drebrin A) during development. In parallel, NMDA receptor (NMDAR)-dependent long-term depression (LTD) of synaptic transmission, induced by low-frequency stimulation (LFS), is dominant in the immature brain and decreases during development. Here, we report that drebrin regulates NMDAR-dependent and group 1 metabotropic glutamate receptor (mGluR)-dependent LTD induction in the hippocampus. While LFS induced NMDAR-dependent LTD in the developing hippocampus in wild-type (WT) mice, it did not induce LTD in developing drebrin E and A double knockout (DXKO) mice, indicating that drebrin is required for NMDAR-dependent LTD. On the other hand, LFS induced robust LTD dependent on mGluR5, one of group 1 mGluRs, in both developing and adult

TY - JOUR. T1 - Activation of metabotropic glutamate receptors induces long-term depression of GABAergic inhibition in hippocampus. AU - Liu, Y. B.. AU - Disterhoft, J. F.. AU - Slater, N. T.. PY - 1993. Y1 - 1993. N2 - 1. The long-term enhancement of synaptic excitability in CA1 hippocampal pyramidal neurons produced by activation of metabotropic glutamate receptors (mGluRs) was studied in rabbit hippocampal slices in vitro. 2. Bath application of the mGluR agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) (5-20 μM) for 20 min produced a reversible depolarization of membrane potentiatil, blockade of spike accommodation, and increase in input resistance of CA1 neurons. However, a long-lasting increase in synaptic excitability was observed: single stimuli applied to the Schaffer collateral commisural fiber pathway evoked epileptiform discharges in the presence of 1S,3R-ACPD and after the washout of 1S,3R-ACPD, persistent paroxysmal depolarization shifts (PDSs) were evoked by ...

Metabotropic glutamate receptor (mGluR) modulation of voltage-gated Ca2+ channels was examined in isolated deep layer frontoparietal cortical neurons under conditions designed to isolate calcium- independent modulatory pathways. Trans-1-aminocyclopentane-1,3- dicarboxylate (t-ACPD), a nonspecific mGluR agonist, produced rapid and reversible inhibition of Ca2+ channels. This effect was mimicked by agonists for group I and group II, but not group III, mGluRs. Effects of group I and II agonists often were observed in the same neurons, but separate subgroups of neurons were unresponsive to the group I agonist quisqualate or the group II agonist 2-(2,3-dicarboxycyclopropyl) glycine (DCG-IV). Inhibition by quisqualate and DCG-IV was nonocclusive in neurons responding to both agonists. These agonists thus appear to act on different mGluRs. The mGluR antagonist alpha-methyl-4- carboxylphenylglycine attenuated inhibition by t-ACPD, quisqualate, and DCG-IV. Inhibition by quisqualate and DCG-IV was ...

Materials. All tissue culture reagents were obtained from Invitrogen (Carlsbad, CA). G418 sulfate was obtained from Mediatech, Inc., (Herndon, VA). [3H]LY341495 (28.28 Ci/mmol) was obtained from American Radiolabeled Chemicals, Inc. (St Louis, MO). l-Glutamate, DCG-IV, l-AP4 [l-(+)-2-amino-4-phosphonobutyric acid], and LY341495 were obtained from Tocris (Ellisville, MO). Methotrexate was purchased from Calbiochem (La Jolla, CA). BINA was synthesized as described previously (Galici et al., 2006). The Calcium 3 Assay Kit was obtained from Molecular Devices (Sunnyvale, CA). The indicator dye fluo-4 was obtained from Invitrogen. Probenecid, dimethyl sulfoxide (DMSO), puromycin dihydrochloride, GDP, and guanosine 5′-3-O-(thio)triphosphate were purchased from Sigma-Aldrich, Inc., (St. Louis, MO). Unifilter-96 GF/B plates and MicroScint-20 were obtained from PerkinElmer Life and Analytical Sciences (Boston, MA). BioCoat poly-d-lysine 96-well culture plates were obtained from BD Biosciences Discovery ...

A family of metabotropic glutamate receptors (mGluRs) has been elucidated by molecular cloning. To study the possible modulatory role of mGluRs in synaptic transmission, we tested the effect of a mGluR agonist, (±)-l-aminocyclopentane-trans-l,3-dicarboxylic acid (trans-ACPD), on the excitatory post-synaptic currents (EPSCS) recorded from neurons in thin slices of rat visual cortex, by using the whole-cell patch-clamp method. We found that trans-ACPD) markedly suppressed the evoked EPSCS without affecting the mean amplitude of spontaneous miniature EPSCS. This effect on the evoked EPSCS was blocked by a potassium channel blocker, 4-aminopyridine (4-AP) in a dose-dependent manner We suggest that trans-ACPD presynaptically inhibits EPSCS by a mechanism involving the 4-AP-sensitive channels. ...

TY - JOUR. T1 - Expression of metabotropic glutamate receptor 8 in autonomic cell groups of the medulla oblongata of the rat. AU - Pamidimukkala, Jaya. AU - Hoang, Caroline J.. AU - Hay, Meredith. PY - 2002/12/6. Y1 - 2002/12/6. N2 - Metabotropic glutamate receptors (mGluRs) in the medulla oblongata have been suggested to have a functional role in the regulation of cardiovascular baroreflexes. The present study examines the localization of mGluR8 autonomic nuclei of the medulla of the rat. mGluR8 immunoreactivity was observed in the cell bodies and/or processes of the dorsolateral, interstitial, medial, intermediate, ventral, ventrolateral, subpostremal, commissural, parvicellular and gelatinosus subnuclei of the nucleus tractus solitarius (NTS). The intensity of mGluR8 staining was highest in the commissural and interstitial subnuclei at the level of the area postrema. Commissural NTS is involved in regulation of baro-, and chemo-reflexes whereas the interstitial nucleus mediates respiratory ...

We use cookies to ensure that we give you the best experience on our website. If you click Continue well assume that you are happy to receive all cookies and you wont see this message again. Click Find out more for information on how to change your cookie settings ...

PubMed Central Canada (PMC Canada) provides free access to a stable and permanent online digital archive of full-text, peer-reviewed health and life sciences research publications. It builds on PubMed Central (PMC), the U.S. National Institutes of Health (NIH) free digital archive of biomedical and life sciences journal literature and is a member of the broader PMC International (PMCI) network of e-repositories.

Thank you for sharing this Journal of Pharmacology and Experimental Therapeutics article.. NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.. ...

Metabotropic glutamate receptors (mGluRs) are coupled to effector systems through GTP-binding proteins (G-proteins) and appear to mediate slow synaptic responses in the CNS. Although mGluR-mediated increases in phosphoinositide hydrolysis have been well characterized, other mechanisms for signal transduction employed by mGluRs are poorly understood. We recently reported that the selective mGluR agonist 1- aminocyclopentane-1 S,3R-dicarboxylic acid (1S,3R-ACPD) increases cAMP accumulation in rat hippocampal slices. We have now investigated the mechanisms involved in this response. A number of G-protein-linked receptors that are not directly coupled to adenylate cyclase increase cAMP accumulation by potentiating cAMP responses to other agonists. Furthermore, previous studies suggest that glutamate increases cAMP accumulation by a mechanism that is dependent upon the presence of endogenous adenosine. Therefore, we tested the hypothesis that 1S,3R- ACPD-stimulated increases in cAMP accumulation in ...

Gentaur molecular products has all kinds of products like :search , FabGennix \ Glutamate Receptor type 5, Antigen blocking peptide \ P-Glur5 for more molecular products just contact us

Drug addiction is a chronic cyclical disease characterized by periods of drug use and abstinence. Drug craving increases as a function of abstinence period, such that longer periods of abstinence result in greater feelings of craving. Longer periods of abstinence may render cues to become more powerful motivators of drug seeking behavior because of the greater craving response. Neurobiological evidence suggests that changes in glutamatergic transmission in the nucleus accumbens (NAc) plays a pivotal role in the incubation of craving and drug seeking motivation. Specifically, the upregulation of Ca²⁺ permeable AMPA receptors may increase drug seeking following the presentation of a drug cue. Environmental housing manipulations also change the expression of metabotropic glutamate receptors (mGlur) and psychostimulant self-administration. In the current experiments, Sprague-Dawley rats were reared in enriched (EC) or isolated (IC) conditions from PND 21-51. Then rats were implanted with ...

TY - JOUR. T1 - Transformation of Receptor Tyrosine Kinases into Glutamate Receptors and Photoreceptors. AU - Leippe, Philipp. AU - Broichhagen, Johannes. AU - Cailliau, Katia. AU - Mougel, Alexandra. AU - Morel, Marion. AU - Dissous, Colette. AU - Trauner, Dirk. AU - Vicogne, Jérôme. PY - 2020/4/20. Y1 - 2020/4/20. N2 - Receptor tyrosine kinases (RTKs) are key regulators of cellular functions in metazoans. In vertebrates, RTKs are mostly activated by polypeptides but are not naturally sensitive to amino acids or light. Taking inspiration from Venus kinase receptors (VKRs), an atypical family of RTKs found in nature, we have transformed the human insulin (hIR) and hepatocyte growth factor receptor (hMET) into glutamate receptors by replacing their extracellular binding domains with the ligand-binding domain of metabotropic glutamate receptor type 2 (mGluR2). We then imparted light sensitivity through covalent attachment of a synthetic glutamate-based photoswitch via a self-labelling SNAP tag. ...

Retrograde synaptic signaling by endocannabinoids (eCBs) is a widespread mechanism for activity-dependent inhibition of synaptic strength in the brain. Although prevalent, the conditions for eliciting eCB-mediated synaptic depression vary among brain circuits. As yet, relatively little is known about the molecular mechanisms underlying this variation, although the initial signaling events are likely dictated by postsynaptic proteins. SAP90/PSD-95-associated proteins (SAPAPs) are a family of postsynaptic proteins unique to excitatory synapses. Using Sapap3 knock-out (KO) mice, we find that, in the absence of SAPAP3, striatal medium spiny neuron (MSN) excitatory synapses exhibit eCB-mediated synaptic depression under conditions that do not normally activate this process. The anomalous synaptic plasticity requires type 5 metabotropic glutamate receptors (mGluR5s), which we find are dysregulated in Sapap3 KO MSNs. Both surface expression and activity of mGluR5s are increased in Sapap3 KO MSNs, ...

Microglia are the immune cell of the central nervous system and become reactive in response to infection or trauma. In Multiple Sclerosis (MS) microglia show early reactivity which may contribute to subsequent neurotoxicity. Glutamate has been implicated in the neurodegeneration in MS. Microglia express subtypes of metabotropic glutamate receptors (mGluRs), the activation of which can lead to microglial evoked neurotoxicity (group II) or neuroprotection (group III). This suggests that release of glutamate from neurones or glial cells may activate microglia via these receptors. Increased microglial reactivity during disease is possibly due to an imbalance of mGluR expression with neurotoxic group II increased above neuroprotective group III mGluRs. Microglial expression of mGluR subtypes was therefore investigated on activated compared with untreated cells. It was found that microglia exposed to myelin expressed increased levels of group II and mGluRl and 8 subtypes compared with control cells. ...

1 Mouse cortical wedge preparations were used in order to study the effects of metabotropic glutamate receptor (mGluR) agonists and antagonists on the depolarization induced by N-methyl-D-aspartate (NMDA) or by (S)-α-amino-4-bromo-3-hydroxy-5-isoxazolepropionic acid (AMPA). 2 (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) (30-300 μM) significantly potentiated the depolarizations induced by NMDA, leaving unchanged those mediated by AMPA. This potentiation developed slowly and lasted for up to 60 min provided that the slices were continuously perfused with the mGluR agonist. 3 Concentration-response curves to NMDA in the absence and in the presence of 1S,3R-ACPD (100 μM) indicated that the potentiation was due to increased affinity of the NMDA receptor complex for its agonist. The maximal responses to NMDA were not potentiated. 4 Selective agonists of group 1 mGluR such as quisqualate (Quis) (30 μM) or (RS)-3,5-dihydroxyphenylglycine (DHPG) (300 μM) did not potentiate NMDA ...

TY - JOUR. T1 - Activation of metabotropic glutamate receptors induces an inward current in rat dopamine mesencephalic neurons. AU - Mercuri, N. B.. AU - Stratta, F.. AU - Calabresi, P.. AU - Bonci, A.. AU - Bernardi, G.. PY - 1993. Y1 - 1993. N2 - To investigate the electrophysiological effects of the stimulation of the metabotropic excitatory amino acid receptors, we applied trans-1-amino-cyclopentane-1,3-dicarboxylate, an agonist of this type of receptors, on presumed rat dopamine cells intracellularly recorded in vitro. Trans-1-amino-cyclopentane-1,3-dicarboxylate (3-30 μM, t-ACPD) caused a sustained increase of the spontaneous firing rate and a depolarization. When the membrane potential was held at about the resting level (-50, -60 mV), by the single-electrode voltage-clamp technique, t-ACPD induced an inward current. In 57% of the tested cells the inward current was associated with a decrease of the apparent input conductance. In the remaining cells no obvious changes in membrane ...

article{6e062fe7-288c-43c8-86d0-a7238940f678, abstract = {In animal models of Parkinsons disease, striatal overactivation of ERK1/2 via dopamine (DA) D1 receptors is the hallmark of a supersensitive molecular response associated with dyskinetic behaviors. Here we investigate the pathways involved in D1 receptor-dependent ERK1/2 activation using acute striatal slices from rodents with unilateral 6-hydroxydopamine (6-OHDA) lesions. Application of the dopamine D1-like receptor agonist SKF38393 induced ERK1/2 phosphorylation and downstream signaling in the DA-denervated but not the intact striatum. This response was mediated through a canonical D1R/PKA/MEK1/2 pathway and independent of ionotropic glutamate receptors but blocked by antagonists of L-type calcium channels. Coapplication of an antagonist of metabotropic glutamate receptor type 5 (mGluR5) or its downstream signaling molecules (PLC, PKC, IP3 receptors) markedly attenuated SKF38393-induced ERK1/2 activation. The role of striatal mGluR5 in ...

TY - JOUR. T1 - In the Telencephalon, GluN2C NMDA Receptor Subunit mRNA is Predominately Expressed in Glial Cells and GluN2D mRNA in Interneurons. AU - Alsaad, Hassan A.. AU - DeKorver, Nicholas W.. AU - Mao, Zhihao. AU - Dravid, Shashank M.. AU - Arikkath, Jyothi. AU - Monaghan, Daniel T.. N1 - Funding Information: Fig. 10 Schematic diagram showing a potential role for GluN2C-containing NMDARs in the tripartite synapse. (1) l-Glutamate released from presynaptic nerve endings activates AMPA receptors and GluN2A-and/or GluN2B-containing NMDARs (NMDAR-2A/2B) on the postsynaptic dendrite. (2) With sufficient synaptic activation, glutamate spillover activates GluN2C-containing NMDARs (NMDAR-2C) and metabotropic glutamate receptors (mGluR) on the astrocyte, leading to increased cytoplasmic calcium levels from extracellular and intracellular sources, respectively. (3) In response to elevated intracellullar calcium from intracellular stores, and possibly from GluN2C currents, astrocytes release ...

Abnormal retinal electrophysiology is present in 80% of patients with DMD. 20 It is characterized by a delayed implicit time and by an amplitude reduction of the b-wave of the electroretinogram (ERG) recorded under scotopic conditions. The b-wave is the sum of the electrical activities of more than one cell type but is believed primarily to reflect the activation of depolarizing bipolar cells. 21 This bipolar depolarization is initiated by a photoreceptor hyperpolarization that results in the a-wave of the ERG. It is also known that the Müller glial cells (MGCs) amplify the b-wave signal of the ERG generated by the bipolar cell. At the cellular level, photoreceptors are depolarized in the dark and continuously release glutamate, the major excitatory transmitter of the CNS. The metabotropic glutamate receptor mGluR6 22 causes depolarized bipolar cells to be hyperpolarized in the dark. When light shines on the retina, photoreceptors hyperpolarize, stopping the Ca2+-dependent release of glutamate ...

TY - JOUR. T1 - Functional partnership between mGlu3 and mGlu5 metabotropic glutamate receptors in the central nervous system. AU - Di Menna, Luisa. AU - Joffe, Max E.. AU - Iacovelli, Luisa. AU - Orlando, Rosamaria. AU - Lindsley, Craig W.. AU - Mairesse, Jèrome. AU - Gressèns, Pierre. AU - Cannella, Milena. AU - Caraci, Filippo. AU - Copani, Agata. AU - Bruno, Valeria. AU - Battaglia, Giuseppe. AU - Conn, P. Jeffrey. AU - Nicoletti, Ferdinando. PY - 2017/10/25. Y1 - 2017/10/25. N2 - mGlu5 receptors are involved in mechanisms of activity-dependent synaptic plasticity, and are targeted by drugs developed for the treatment of CNS disorders. We report that mGlu3 receptors, which are traditionally linked to the control of neurotransmitter release, support mGlu5 receptor signaling in neurons and largely contribute to the robust mGlu5 receptor-mediated polyphosphoinositide hydrolysis in the early postnatal life. In cortical pyramidal neurons, mGlu3 receptor activation potentiated mGlu5 ...

The overall goals of this proposal are to quantitatively characterize the effects on neural activation and cerebral networks of novel compounds that target meta...

Clinical Trials - clinicaltrials.gov This noninterventional study will assess genomic changes in the metabotropic glutamate receptor (mGluR) network in children...

The metabotropic glutamate receptors (mGluRs) are key receptors in the modulation of excitatory synaptic transmission in the central nervous system. Here we have determined three different crystal structures of the extracellular ligand-binding region of mGluR1--in a complex with glutamate and in two …

Astellas Pharma is undertaking a research programme into noncompetitive metabotropic glutamate receptor type 1 (mGluR1) antagonists for the potential treatment

Close The Infona portal uses cookies, i.e. strings of text saved by a browser on the users device. The portal can access those files and use them to remember the users data, such as their chosen settings (screen view, interface language, etc.), or their login data. By using the Infona portal the user accepts automatic saving and using this information for portal operation purposes. More information on the subject can be found in the Privacy Policy and Terms of Service. By closing this window the user confirms that they have read the information on cookie usage, and they accept the privacy policy and the way cookies are used by the portal. You can change the cookie settings in your browser. ...

4OO9: Structure of the human class C GPCR metabotropic glutamate receptor 5 transmembrane domain in complex with the negative allosteric modulator mavoglurant

Engers DW, Blobaum AL, Gogliotti RD, Cheung YY, Salovich JM, Garcia-Barrantes PM, Daniels JS, Morrison R, Jones CK, Soars MG, Zhuo X, Hurley J, Macor JE, Bronson JJ, Conn PJ, Lindsley CW, Niswender CM, Hopkins CR (2016). Discovery, Synthesis, and Preclinical Characterization of N-(3-Chloro-4-fluorophenyl)-1H-pyrazolo[4,3-b]pyridin-3-amine (VU0418506), a Novel Positive Allosteric Modulator of the Metabotropic Glutamate Receptor 4 (mGlu4). ACS Chem Neurosci. 7: 1192-200. doi:10.1021/acschemneuro.6b00035. PMID 27075300 ...

Fragile X syndrome is caused by lack of fragile X mental retardation protein (FMRP) due to silencing of the FMR1 gene. The metabotropic glutamate receptors (mGluRs) in the central nervous system contribute to higher brain functions including learning/memory, mental disorders and persistent pain. The transcription factor cyclic AMP-responsive element binding protein (CREB) is involved in important neuronal functions, such as synaptic plasticity and neuronal survival. Our recent study has shown that stimulation of Group I mGluRs upregulated FMRP and activated CREB in anterior cingulate cortex (ACC), a key region for brain cognitive and executive functions, suggesting that activation of Group I mGluRs may upregulate FMRP through CREB signaling pathway. In this study, we demonstrate that CREB contributes to the regulation of FMRP by Group I mGluRs. In ACC neurons of adult mice overexpressing dominant active CREB mutant, the upregulation of FMRP by stimulating Group I mGluR is enhanced compared to wild-type

TY - JOUR. T1 - A slow excitatory postsynaptic current mediated by G-protein-coupled metabotropic glutamate receptors in rat ventral tegmental dopamine neurons. AU - Johnson, Steven W.. PY - 1997/2/28. Y1 - 1997/2/28. N2 - Dopamine neurons in the substantia nigra and ventral tegmental area express metabotropic glutamate receptors, but activation of these receptors by synaptic release of neurotransmitter has not been demonstrated thus far. Patch pipettes were used to record membrane currents under voltage clamp from presumed dopamine-containing neurons in the whole-cell configuration in the rat brain slice. A short train of electrical stimuli delivered to bipolar electrodes placed in the slice evoked a slow excitatory postsynaptic current (EPSC; 50-300 pA at -70 mV) which peaked 560 ms after onset and lasted several seconds, with a decay time-constant of 630 ms. This slow EPSC was voltage-dependent, and was abolished by tetrodotoxin (0.5 μM) or by perfusate containing low calcium (0.5 mM) and ...

Aims: The purpose of this study was to investigate the association between the metabotropic glutamate receptor 3 (GRM3) subunit gene and alcohol dependence by the single-nucleotide polymorphisms (SNPs). Methods: Two hundred and forty-eight male alcohol-dependent patients and 235 male control subjects were recruited. Ten SNPs in the GRM3 region were studied, and genotyping of SNPs was performed by ligase detection reactions. Results: We found highly significant differences in allele and genotype frequencies of rs6465084 between the alcohol-dependent and control group, with the greater frequency of A allele of SNP rs6465084 in alcohol-dependent group. We also found significant differences of haplotype frequencies in five combinations (including TAATATT, CAGTATT, TCGTATT, CAATAGC, TAATATC) in the linkage disequilibrium constructed by seven SNPs between the groups. Conclusion: Our results supplied the first evidence that the polymorphism of GRM3 gene associates with the morbidity of alcohol ...

Science & Technology, Life Sciences & Biomedicine, Clinical Neurology, Neurosciences, Neurosciences & Neurology, CLINICAL NEUROLOGY, NEUROSCIENCES, metabotropic glutamate receptor, dorsal root reflex, 4-AP, arthritis, pain, CENTRAL-NERVOUS-SYSTEM, AMINO-ACID RELEASE, MESSENGER-RNA, IN-VIVO, NOCICEPTIVE TRANSMISSION, PERIPHERAL INFLAMMATION, MONOSYNAPTIC EXCITATION, JOINT INFLAMMATION, HORN NEURONS, CORD NEURONS ...

It has been proposed that metabotropic glutamate receptor-dependent long-term depression (mGluR-LTD) can reverse cocaine-evoked synaptic plasticity in the ventral tegmental area (VTA). Mameli et al. have now unraveled the expression mechanism of mGluR-LTD in the VTA of mice exposed to a single dose of cocaine. LTD in this system is not due to the simple removal of AMPA receptors (AMPARs) from the synapse. Instead, AMPARs are replaced by new ones that contain newly synthesized GluR2 subunits. The synapse thus expresses LTD not because there are fewer receptors but because the conductance of the new GluR2-containing AMPARs is reduced.. M. Mameli, B. Balland, R. Luján, C. Lüscher, Rapid synthesis and synaptic insertion of GluR2 for mGluR-LTD in the ventral tegmental area. Science 317, 530-533 (2007). [Abstract] [Full Text] ...

Use-dependent downregulation of neuronal activity (negative feedback) can act as a homeostatic mechanism to maintain neuronal activity at a particular specified value. Disruption of this negative feedback might lead to neurological pathologies such as epilepsy, but the precise mechanisms by which this feedback can occur remain incompletely understood. At one glutamatergic synapse, the Drosophila neuromuscular junction, a mutation in the group II metabotropic glutamate receptor gene ( DmGluRA ) increased motor neuron excitability by disrupting an autocrine, glutamate-mediated negative feedback. I show that DmGluRA mutations increase neuronal excitability by preventing PI3 kinase (PI3K) activation and consequently hyperactivating the transcription factor Foxo. Furthermore, glutamate application increases levels of phospho-Akt, a product of PI3K signaling, within motor nerve terminals in a DmGluRA -dependent manner. Finally, I show that PI3K increases both axon diameter and synapse number via the ...

TY - JOUR. T1 - Vagal afferent fibres determine the oxytocin-induced modulation of gastric tone. AU - Holmes, Gregory M.. AU - Browning, Kirsteen N.. AU - Babic, Tanja. AU - Fortna, Samuel R.. AU - Coleman, F. Holly. AU - Travagli, R. Alberto. PY - 2013/6/1. Y1 - 2013/6/1. N2 - Oxytocin (OXT) inputs to the dorsal vagal complex (DVC; nucleus of the tractus solitarius (NTS) dorsal motor nucleus of the vagus (DMV) and area postrema) decrease gastric tone and motility. Our first aim was to investigate the mechanism(s) of OXT-induced gastric relaxation. We demonstrated recently that vagal afferent inputs modulate NTS-DMV synapses involved in gastric and pancreatic reflexes via group II metabotropic glutamate receptors (mGluRs). Our second aim was to investigate whether group II mGluRs similarly influence the response of vagal motoneurons to OXT. Microinjection of OXT in the DVC decreased gastric tone in a dose-dependent manner. The OXT-induced gastric relaxation was enhanced following bethanechol and ...

PubMed Listing. Fox IK, Schwetye KE, Keune JD, Brenner MJ, Yu JW, Hunter DA, Wood PM, Mackinnon SE. Schwann-cell injection of cold-preserved nerve allografts. Microsurgery. 2005; 25(6):502-7. Keune JD, Brenner MJ, Schwetye KE, Yu JW, Fox IK, Hunter DA, Mackinnon SE. Temporal factors in peripheral nerve reconstruction with suture scaffolds: an experimental study in rodents. Restor Neurol Neurosci. 2006;24(3):181-90. Hartman RE, Shah A, Fagan AM, Schwetye KE, Parsadanian M, Schulman RN, Finn MB, Holtzman DM. Pomegranate juice decreases amyloid load and improves behavior in a mouse model of Alzheimers disease. Neurobiol Dis. 2006 Dec; 24(3):506-15. Jong YJ*, Schwetye KE*, OMalley KL. J Neurochem. Nuclear localization of functional metabotropic glutamate receptor mGlu1 in HEK293 cells and cortical neurons: role in nuclear calcium mobilization and development. 2007 Apr; 101(2):458-69. (*co-first authors) Brody DL, Mac Donald C, Kessens CC, Yuede C, Parsadanian M, Spinner M, Kim E, Schwetye KE, ...

We are pleased to inform you that Neuroimmunology at Queen Elizabeth University Hospital Glasgow is now able to offer testing for Anti- glutamate receptor (Type NMDA) antibodies and Anti- voltage gated potassium channel associated proteins (LGI1 and CASPR2).. •Anti- glutamate receptor (Type NMDA) antibodies Anti-NMDA receptor encephalitis manifests along a spectrum of psychosis, altered behaviour, movement disorder, seizures, autonomic dysfunction and decreased consciousness. In younger patients, particularly female, it is associated with an underlying teratoma. Early identification and treatment with immunotherapy leads to better outcomes (Pubmed ID 23290630). It is less common in older patients (over 45 years old) and they display a less severe phenotype and have poorer outcomes (Pubmed ID23946310).. Antibodies against the NR1 subunit of the NMDA receptor are identified in our laboratory via indirect immunofluorescence of cell lines transfected with cDNA coding this protein. This test has ...

Clearance of extracellular glutamate is essential for limiting the activity of metabotropic glutamate receptors (mGluRs) at excitatory synapses; however, the relative contribution of transporters found in neuronal and glial membranes to this uptake is poorly understood. Hippocampalinterneurons located at the oriens-alveus border express mGluR1alpha, a metabotropic glutamate receptor that regulates excitability and synaptic plasticity. To determine which glutamate transporters are essential for removing glutamate at these excitatory synapses, we recorded mGluR1-mediated EPSCs from oriens-lacunosum moleculare (O-LM) interneurons in acute hippocampal slices. Stimulation in stratum oriens reliably elicited a slow mGluR1-mediated current in O-LM interneurons if they were briefly depolarized to allow Ca2+ entry before stimulation. Selective inhibition of GLT-1 [for glutamate transporter; EAAT2 (for excitatory amino acid transporter)] with dihydrokainate increased the amplitude of these responses ...

Glutamate is an amino acid that acts as a neurotransmitter in the Central Nervous System. It is associated with neural communication, memory formation, and learning. Glutamate receptors are also implicated in a number of neurodegenerative diseases. Exposure to toxins, old age, congenital predisposition, and brain trauma can trigger glutamate receptor activation and ensuing neurodegeneration. Ionotropic glutamate receptors form the ion channel pore that activates when glutamate binds to the receptor. There are also many subtypes of extracellular glutamate receptors that bind to some chemicals more selectively than to glutamate. Sigma-Aldrich offers monoclonal and polyclonal antibodies that act on glutamate receptors. They are reactive in human, rat, and other species, with various applications.

Schizophrenia is a serious psychiatric disorder that affects 1% of the population. Current theories implicate NMDA receptor hypofunction as a contributor to the symptomology and pathological alterations in schizophrenia. Cognitive impairments are increasingly recognized as not only fundamental to schizophrenia, but the strongest predictor of patient functional outcomes. Current antipsychotics do not improve the cognitive symptoms of the disorder; however, recent efforts have resulted in the identification of novel drug targets. One target is metabotropic glutamate receptors as they interact with and modulate NMDA receptors. Another approach focuses on dopamine, the neurotransmitter system targeted by traditional antipsychotics. Tetrahydroprotoberberines, such as D- and L-govadine, are synthetic compounds derived from traditional medicine that have demonstrated efficacy in treating schizophrenic symptoms. The present study assessed the effects of CDPPB (a metabotropic glutamate receptor 5 ...

PubMed Central Canada (PMC Canada) provides free access to a stable and permanent online digital archive of full-text, peer-reviewed health and life sciences research publications. It builds on PubMed Central (PMC), the U.S. National Institutes of Health (NIH) free digital archive of biomedical and life sciences journal literature and is a member of the broader PMC International (PMCI) network of e-repositories.

Glutamate Receptors: Cell-surface proteins that bind glutamate and trigger changes which influence the behavior of cells. Glutamate receptors include ionotropic receptors (AMPA, kainate, and N-methyl-D-aspartate receptors), which directly control ion channels, and metabotropic receptors which act through second messenger systems. Glutamate receptors are the most common mediators of fast excitatory synaptic transmission in the central nervous system. They have also been implicated in the mechanisms of memory and of many diseases.

Positive allosteric modulators of the ionotropic glutamate receptor-2 (GluA2) are promising compounds for the treatment of cognitive disorders, e.g. Alzheimers disease. These modulators bind within the dimer interface of the LBD (ligand-binding domain) and stabilize the agonist-bound conformation slowing receptor desensitization and/or deactivation. In the present study, we employ isothermal titration calorimetry to determine binding affinities and thermodynamic details of binding of modulators of GluA2. A mutant of the LBD of GluA2 (LBD-L483Y-N754S) that forms a stable dimer in solution was used. The potent GluA2 modulator BPAM-97 was used as a reference compound. Evidence that BPAM-97 binds in the same pocket as the well-known GluA2 modulator cyclothiazide was obtained from X-ray structures. The LBD-L483Y-N754S:BPAM-97 complex has a Kd of 5.6 μM (ΔH=−4.9 kcal/mol, −TΔS=−2.3 kcal/mol; where 1 kcal≈4.187 kJ). BPAM-97 was used in a displacement assay to determine a Kd of 0.46 mM ...

This new protein, termed Opto-mGluR6, is a chimeric protein that consists of two local retinal proteins: the light-sensing domains of the retinal photopigment melanopsin and the signaling domain of the metabotropic glutamate receptor 6 (mGluR6). mGluR6 is a protein found in retinal ON-bipolar cells that is naturally activated by the neurotransmitter glutamate released from the photoreceptors, thereby amplifying the incoming signal.. Because ON-bipolar cells naturally receive direct input from the photoreceptors, turning the native chemically activated receptor mGluR6 into a light-activated receptor means that signaling mechanisms in the ON-bipolar cells are preserved, conferring high light-sensitivity and fast normal responsiveness. And using the extracellular domain of melanopsin as a light antenna provides resistance to bleaching: No matter how hard the protein is hit by light, the response of Opto-mGluR6 never attenuates.. To demonstrate the therapeutic potential of this new tool, the ...

TY - JOUR. T1 - Human Ca2+ receptor cysteine-rich domain. T2 - Analysis of function of mutant and chimeric receptors. AU - Hu, Jianxin. AU - Hauache, Omar. AU - Spiegel, Allen M.. PY - 2000/5/26. Y1 - 2000/5/26. N2 - The 612-residue extracellular domain of the human Ca2+ receptor (hCaR) has been speculated to consist of a Venuss-flytrap domain (VFT) and a cysteine-rich domain. We studied the function of the hCaR Cys-rich domain by using mutagenesis and chimera approaches. A chimeric hCaR with the sequence from residues 540-601 replaced by the corresponding sequence from the Fugu CaR remained fully functional. Another chimetic hCaR with the same region of sequence replaced by the corresponding sequence from metabotropic glutamate receptor subtype 1 (mGluR1) still was activated by extracellular Ca2+ ([Ca2+](o)), but its function was severely compromised. Chimeric receptors with the hCaR VFT and mGluR1 seven-transmembrane domain plus C-tail domain retained good response to [Ca2+](o) whether the ...

Buy (S)-3,5-DHPG (CAS 162870-29-3), a water soluble selective group I mGluR agonist cited in 20 publications. Join researchers using high quality (S)-3,5-DHPG…

Alfa Aesar™ D-(-)-2-Phenylglycine chloride hydrochloride, 98% 5g Alfa Aesar™ D-(-)-2-Phenylglycine chloride hydrochloride, 98% Amino Acids

2-Phenylglycine (DL-α-Phenylglycine) is a metabolite in breast milk during the W2 to W4 lactation period. - Mechanism of Action & Protocol.

Long-term depression (LTD), in neurophysiology, is an activity-dependent reduction in the efficacy of neuronal synapses lasting hours or longer following a long patterned stimulus. LTD occurs in many areas of the CNS with varying mechanisms depending upon brain region and developmental progress. LTD in the hippocampus and cerebellum have been the best characterized, but there are other brain areas in which mechanisms of LTD are understood. LTD has also been found to occur in different types of neurons that release various neurotransmitters, however, the most common neurotransmitter involved in LTD is L-glutamate. L-glutamate acts on the N-methyl-D- asparate receptors (NMDARs), α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs), kainate receptors (KARs) and metabotropic glutamate receptors (mGluRs) during LTD. It can result from strong synaptic stimulation (as occurs in the cerebellar Purkinje cells) or from persistent weak synaptic stimulation (as in the hippocampus). ...

How is Glutamate Receptor Ionotropic Kainate 1 abbreviated? GRIK1 stands for Glutamate Receptor Ionotropic Kainate 1. GRIK1 is defined as Glutamate Receptor Ionotropic Kainate 1 somewhat frequently.

How is Glutamate Receptor, Ionotropic, Kainate 3 abbreviated? GRIK3 stands for Glutamate Receptor, Ionotropic, Kainate 3. GRIK3 is defined as Glutamate Receptor, Ionotropic, Kainate 3 somewhat frequently.

Kim et al report the identification of DGKζ as an interactor of the postsynaptic density‐associated protein PSD95, which is a major scaffolding protein concentrated in dendritic spines. These structures are dynamic actin‐rich protrusions of neuronal dendrites that are characteristic of excitatory neurons and receive inputs from other neurons presynaptic terminals (Newpher and Ehlers, 2008). Spines are, thus, primary sites of signal integration, in which a variety of receptors and receptor‐channels modulate synaptic strength and plasticity, with intracellular Ca2+ as a major player. PSD‐95 family members regulate the function, traffic and signalling downstream of glutamate receptors, such as AMPA, NMDA and PLC‐coupled metabotropic glutamate receptors 1 and 5 (AMPAR, NMDAR, mGluR1 and mGluR5, respectively). After demonstrating the dependency of DGKζ on PSD‐95 for its proper targeting at dendritic spines, Kim et al examined the relevance of this interaction for synaptic physiology. ...

Various GABAergic neuron types of the amygdala cooperate to control principal cell firing during fear-related and other behaviors, and understanding their specialized roles is important. Among GABAergic neurons, the so-called intercalated cells (ITCcs) are critically involved in the expression and extinction of fear memory. Tightly clustered small-sized spiny neurons constitute the majority of ITCcs, but they are surrounded by sparse, larger neurons (L-ITCcs) for which very little information is known. We report here a detailed neurochemical, structural and physiological characterization of rat L-ITCcs, as identified with juxtacellular recording/labeling in vivo. We supplement these data with anatomical and neurochemical analyses of nonrecorded L-ITCcs. We demonstrate that L-ITCcs are GABAergic, and strongly express metabotropic glutamate receptor 1α and GABAA receptor α1 subunit, together with moderate levels of parvalbumin. Furthermore, L-ITCcs are innervated by fibers enriched with metabotropic

Oriens-lacunosum moleculare (OLM) cells are hippocampal inhibitory interneurons that have been implicated in regulation of information flow and synaptic plasticity in the CA1 circuit. Since anatomical evidence indicates that OLM cells express metabotopic cholinergic (mAChR) and glutamatergic (mGluR) receptors, such modulation of these cells may contribute to switching between functional modes of the hippocampus. Using a transgenic mouse line to identify the Chrna2-positive OLM cells, we investigated metabotropic neuromodulation of intrinsic properties of OLM cells. We found that both mAChR and mGluR activation increased the spontaneous action potential rate and caused the cells to exhibit long-lasting depolarizing plateau potentials following evoked spike trains. Both the mAChR- and mGluR-induced increased spontaneous firing rate and plateau potentials were dependent on intracellular calcium, and were eliminated by blocking Ca2+-dependent transient receptor potential (TRP) cation channels. At ...

Layer 4 of the sensory neocortex receives widespread convergent inputs from thalamic, intracortical, and corticocortical sources. Yet, the relative information bearing roles for most of these pathways remain largely undefined. Here we show that the intracortical projections from layer 6 to layer 4 exhibit a physiological property that is consistent with a modulator role. Using in vitro slice preparations of the auditory and somatosensory cortices, we found that electrical stimulation or photostimulation of layer 6 elicits a prolonged depolarizing response that is attributable to the activation of group 1 metabotropic glutamate receptors (mGluRs). These results complement the known physiological properties of the layer 6 to layer 4 pathway, and further suggest that this pathway is not a principle conduit for information flow, but rather acts as a modulator of cortical activity.

C. Millán, R. Luján, R. Shigemoto, and J. Sánchez Prieto, The inhibition of glutamate release by metabotropic glutamate receptor 7 affects both [Ca2+]c and cAMP. Evidence for a strong reduction of Ca2+ entry in single nerve terminals, Journal of Biological Chemistry, vol. 277, no. 16, pp. 14092-14101, 2002 ...

from neuron import h # metabotropic glutamate receptor class SynapsemGLUR: def __init__(self,sect,loc): self.syn = h.mGLUR(loc, sec=sect) # AMPA synapse with calcium influx -- mechanism defined in mod/ampa_forti.mod class SynapseAMPACA: def __init__(self, sect, loc, e): self.syn = h.AmpaSyn(loc, sec=sect) self.syn.e = e # NMDA synapse with calcium influx -- mechanism defined in mod/nmda_andr.mod class SynapseNMDACA: def __init__(self, sect, loc, e): self.syn = h.NmdaSyn(loc, sec=sect) self.syn.e = e class Synapse: def __init__(self, sect, loc, tau1, tau2, e): self.syn = h.MyExp2SynBB(loc, sec=sect) self.syn.tau1 = tau1 self.syn.tau2 = tau2 self.syn.e = e class SynapseNMDA: def __init__(self, sect, loc, tau1NMDA, tau2NMDA, r, e): self.syn = h.MyExp2SynNMDABB(loc, sec=sect) self.syn.tau1NMDA = tau1NMDA self.syn.tau2NMDA = tau2NMDA self.syn.r = r self.syn.e = e # gabab based on 1995 PNAS paper by Destexhe class SynapseGABAB: def __init__(self, sect, loc): self.syn = h.GABAB(loc, sec=sect) class ...

Importance Genetic markers at the gene encoding the metabotropic glutamate receptor 3 (GRM3) showed allelic association with bipolar disorder. Objective To screen the GRM3 gene and adjacent control regions of genomic DNA in volunteers with bipolar affective disorder for mutations increasing susceptibility to bipolar disorder. Design Sequencing and high-resolution melting curve analysis of DNA followed by genotyping was carried out in 1099 patients with bipolar affective disorder and 1152 healthy comparator individuals ...

Levitz will be presenting a system in which G-protein-coupled receptors, molecules that play key roles in transmitting signals within cells, can be selectively activated. He is planning to use the system to study the hippocampus, a region of the brain where memories are formed, stored and maintained. There may be clinical utility to the system as well, he points out. G-protein-coupled receptors are also critical for vision in the retina, and light-sensing versions could potentially be introduced into people with damaged retinas in order to restore sight.. The presentation, Design and Application of a Light-Activated Metabotropic Glutamate Receptor for Optical Control of Intracellular Signaling Pathways will be presented at 8:30 a.m. on March 7, 2011 in Room 309 of the Baltimore Convention Center. ABSTRACT: http://tinyurl.com/4lf9dse. The research was funded by the Nanomedicine Development Center at the National Institutes of Health.. ...

Overview of Interests. Dr. Fergusons research is focused on the functional regulation and activity of G protein-coupled receptors (GPCRs) as a consequence of their interactions with other proteins expressed inside and outside of the cell and how these interactions regulate both normal pathological cell signaling. His current research efforts are primarily focused on the role of metabotropic glutamate receptor signaling in Huntingtons, Alzheimers and Parkinsons disease, the regulation of serotonin receptor activity by corticotrophin releasing factor receptors in response stress with a goal of understanding the effect stress has on anxiety and depression behaviours, as well as understanding the molecular changes in GPCR signaling associated with hypertension.. Research Achievements. Dr. Ferguson was the first to identify beta-arrestins as endocytic adaptor proteins for GPCRs and to show that they contribute to the coupling of GPCRs to G protein-independent signal transduction pathways. His ...

We have explored membrane-initiated estradiol signaling in several other systems, as well. For example, in dorsal root ganglion cells, ATP acts as a nociceptive messenger. In these cells, estradiol activates an ERα that is coupled to a metabotropic glutamate receptor that inhibits L-type voltage gated Ca2+ channels (VSCC) and attenuates the influx of calcium - thus, potentially attenuating painful signals. In a second system, the dopaminergic neurons of the substantia nigra, estradiol membrane signaling is mediated by another estrogen receptor, ERβ. Here, estradiol is neuroprotective and interacts with the IGF-1 system by activation of the phosphatidyl-inositol-3-kinase/Akt (PI3K/Akt) pathway. Estradiol acts both on neurons and through astrocytes to alter the ratio of anti-inflammatory to pro-inflammatory cytokines released may serve to protect against Parkinsons disease. ...

G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups [(PUBMED:12679517)]. The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence [(PUBMED:8170923)]. The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) [(PUBMED:8170923), (PUBMED:8081729), (PUBMED:15914470), (PUBMED:18948278), (PUBMED:16753280)]. GPCRs are major drug targets, and are consequently ...

G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups [(PUBMED:12679517)]. The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence [(PUBMED:8170923)]. The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) [(PUBMED:8170923), (PUBMED:8081729), (PUBMED:15914470), (PUBMED:18948278), (PUBMED:16753280)]. GPCRs are major drug targets, and are consequently ...

PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Millán, C., Castro, E., Torres, M., Shigemoto, R., & Sánchez Prieto, J. (2003). Co-expression of metabotropic glutamate receptor 7 and N-type Ca2+ channels in single cerebrocortical nerve terminals of adult rats. Journal of Biological Chemistry. American Society for Biochemistry and Molecular Biology. https://doi.org/10.1074/jbc.M211471200 ...

Close The Infona portal uses cookies, i.e. strings of text saved by a browser on the users device. The portal can access those files and use them to remember the users data, such as their chosen settings (screen view, interface language, etc.), or their login data. By using the Infona portal the user accepts automatic saving and using this information for portal operation purposes. More information on the subject can be found in the Privacy Policy and Terms of Service. By closing this window the user confirms that they have read the information on cookie usage, and they accept the privacy policy and the way cookies are used by the portal. You can change the cookie settings in your browser. ...

The glutamatergic mGlu5 receptor and the purinergic P2Y12 receptor are two important targets in the development of novel treatments of gastroesophageal reflux disease (GERD) and thrombosis, respectively. Synthesis was developed to investigate the structure-activity relationships (SAR) of a novel series of 2-alkynylpyridine derivatives as mGluR5 antagonists. This led to the discovery of antagonists with potency in the low-nanomolar range. High microsomal metabolism, possibly due to high lipophilicity, remained an issue. Further, SAR development for a series of ethyl 6-piperazinylnicotinates, featured by a urea linker, as antagonists of the P2Y12 receptor showed the 3-ethoxycarbonyl substituent as central to binding. The low aqueous solubility was addressed by variation of the linker which led to the discovery of sulfonylureas as P2Y12 antagonists. The chemical stability of the sulfonylurea compounds during prolonged storage in solution was found to be related to the sulfonyl urea linker and ...

Glutamate Receptor 6 Lysates available through Novus Biologicals. Browse our Glutamate Receptor 6 Lysate catalog backed by our Guarantee+.

In order to characterize expression of Homers in mouse brain and peripheral tissues we have developed a coupled reverse transcription (RT)-PCR/restriction digestion approach. This has allowed us to determine the molecular composition and relative levels of the constitutive expression of the Homer-1, -2 and -3 mRNAs across mouse tissues. We report here that mammalian brain constitutively expresses high levels of the Homer-1, -2 and -3 mRNAs. Expression of the Homer-1 mRNAs reaches 66% of the brain total Homer mRNAs expression, followed by Homer-3 mRNA (22%) and Homer-2 mRNAs (12%). Quantitative RT-PCR analysis and the Western blotting using pan-Homer antibody revealed that mouse heart, skeletal muscle and diaphragm constitutively express high levels of the Homer proteins and their mRNAs. We have shown that the molecular profile of expression of Homer-1, -2 and -3 mRNAs in muscle containing tissues resembles that obtained for mammalian brain.