Cellular and subcellular localization of metabotropic glutamate (mGlu) receptor 4 in the rodent amygdala

2014 ◽  
Vol 2 (Suppl. 1) ◽  
pp. A1.32
Author(s):  
Sara Ferrazzo
Keyword(s):  
Subcellular Localization ◽  
Mglu Receptor ◽  
Metabotropic Glutamate

Insights into the Structural Aspects of the mGlu Receptor Orthosteric Binding Site

2019 ◽  
Vol 19 (26) ◽  
pp. 2421-2446 ◽  
Author(s):  
Junliang Hao ◽  
Qi Chen
Keyword(s):  
Binding Pocket ◽  
Receptor Subtypes ◽  
X Ray ◽  
Mglu Receptor ◽  
Metabotropic Glutamate ◽  
Amino Terminal ◽  
Subtype Selectivity ◽  
Agonist And Antagonist ◽  
Amino Terminal Domain ◽  
Structural Aspects

The amino terminal domain (ATD) of the metabotropic glutamate (mGlu) receptors contains the orthosteric glutamate recognition site, which is highly conserved across the eight mGlu receptor subtypes. In total, 29 X-ray crystal structures of the mGlu ATD proteins have been reported to date. These structures span across 3 subgroups and 6 subtypes, and include apo, agonist- and antagonist-bound structures. We will discuss the insights gained from the analysis of these structures with the focus on the interactions contributing to the observed group and subtype selectivity for select agonists. Furthermore, we will define the full expanded orthosteric ligand binding pocket (LBP) of the mGlu receptors, and discuss the macroscopic features of the mGlu ATD proteins.

[3H]-LY341495 as a novel antagonist radioligand for group II metabotropic glutamate (mGlu) receptors: characterization of binding to membranes of mGlu receptor subtype expressing cells

1999 ◽  
Vol 38 (10) ◽  
pp. 1519-1529 ◽  
Author(s):  
Bryan G Johnson ◽  
Rebecca A Wright ◽  
M.Brian Arnold ◽  
William J Wheeler ◽  
Paul L Ornstein ◽  
...  
Keyword(s):  
Receptor Subtype ◽  
Mglu Receptor ◽  
Metabotropic Glutamate ◽  
Group Ii

Synthesis and biological evaluation of (−)-kainic acid analogues as phospholipase D-coupled metabotropic glutamate receptor ligands

2014 ◽  
Vol 12 (47) ◽  
pp. 9638-9643 ◽  
Author(s):  
Chiara Zanato ◽  
Sonia Watson ◽  
Guy S. Bewick ◽  
William T. A. Harrison ◽  
Matteo Zanda
Keyword(s):  
Kainic Acid ◽  
Glutamate Receptor ◽  
Phospholipase D ◽  
Metabotropic Glutamate Receptor ◽  
Muscle Spindles ◽  
Biological Evaluation ◽  
Receptor Ligands ◽  
Mglu Receptor ◽  
Metabotropic Glutamate ◽  
Synthesis And Biological Evaluation

A “click” 4-(1,2,3-triazolyl)-kainate derivative and its biotinylated version potently increase stretch-induced afferent firing in muscle spindles, probably acting through a hitherto uncloned phospholipase D (PLD)-coupled mGlu receptor.

Epileptogenesis Up-Regulates Metabotropic Glutamate Receptor Activation of Sodium-Calcium Exchange Current in the Amygdala

2000 ◽  
Vol 83 (4) ◽  
pp. 2458-2462 ◽  
Author(s):  
N. Bradley Keele ◽  
Fatiha Zinebi ◽  
Volker Neugebauer ◽  
P. Shinnick-Gallagher
Keyword(s):  
Basolateral Amygdala ◽  
Metabotropic Glutamate Receptor ◽  
Partial Agonist ◽  
Brain Slices ◽  
Receptor Activation ◽  
Exchange Current ◽  
Inward Current ◽  
Mglu Receptor ◽  
Metabotropic Glutamate ◽  
Group I

Postsynaptic metabotropic glutamate (mGlu) receptor-activated inward current mediated by Na+-Ca2+ exchange was compared in basolateral amygdala (BLA) neurons from brain slices of control (naı̈ve and sham-operated) and amygdala-kindled rats. In control neurons, the mGlu agonist, quisqualate (QUIS; 1–100 μM), evoked an inward current not associated with a significant change in membrane slope conductance, measured from current-voltage relationships between −110 and −60 mV, consistent with activation of the Na+-Ca2+ exchanger. Application of the group I selective mGlu receptor agonist ( S)-3,5-dihydroxyphenylglycine [( S)-DHPG; 10–1000 μM] or the endogenous agonist, glutamate (10–1000 μM), elicited the exchange current. QUIS was more potent than either ( S)-DHPG or glutamate (apparent EC50 = 19 μM, 57 μM, and 0.6 mM, respectively) in activating the Na+-Ca2+ exchange current. The selective mGlu5 agonist, ( R,S)-2-chloro-5-hydroxyphenylglycine [( R,S)-CHPG; apparent EC50 = 2.6 mM] also induced the exchange current. The maximum response to ( R,S) -DHPG was about half of that of the other agonists suggesting partial agonist action. Concentration-response relationships of agonist-evoked inward currents were compared in control neurons and in neurons from kindled animals. The maximum value for the concentration-response relationship of the partial agonist ( S)-DHPG- (but not the full agonist- [QUIS or ( R, S)-CHPG]) induced inward current was shifted upward suggesting enhanced efficacy of this agonist in kindled neurons. Altogether, these data are consistent with a kindling-induced up-regulation of a group I mGlu-, possibly mGlu5-, mediated responses coupled to Na+-Ca2+ exchange in BLA neurons.

Cellular, and subcellular localization of the mGluR5a metabotropic glutamate receptor in rat spinal cord

Neuroreport ◽  
1994 ◽  
Vol 6 (1) ◽  
pp. 209-213 ◽  
Author(s):  
Zoltan Vidnyánszky ◽  
József Hamori ◽  
Lászlo Négyessy ◽  
Doris Rüegg ◽  
Thomas Knopfel ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Subcellular Localization ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Rat Spinal Cord ◽  
Metabotropic Glutamate

Metabotropic glutamate receptor activation induces calcium waves within hippocampal dendrites

1994 ◽  
Vol 72 (1) ◽  
pp. 471-474 ◽  
Author(s):  
D. B. Jaffe ◽  
T. H. Brown
Keyword(s):  
Action Potentials ◽  
Pyramidal Neurons ◽  
Metabotropic Glutamate Receptor ◽  
Threshold Level ◽  
Receptor Activation ◽  
Confocal Imaging ◽  
Voltage Gated ◽  
Mglu Receptor ◽  
Metabotropic Glutamate ◽  
Cell Recording

1. We investigated the effects of metabotropic glutamate (mGlu) receptor activation on intracellular Ca2+ concentration ([Ca2+]i) in the soma and dendrites of hippocampal CA1 pyramidal neurons. Changes in [Ca2+]i were measured using confocal imaging simultaneously with whole-cell recording techniques. Differences in [Ca2+]i were visualized as changes in the fluorescence of the Ca(2+)-sensitive dye Fluo-3. 2. Brief application of the specific mGlu receptor agonist (1S,3R)-ACPD to either the apical or basal dendrites produced initially localized increases in [Ca2+]i that subsequently propagated as waves throughout much of the neuron. These Ca2+ waves, which propagated at approximately 40 microns/s, were shown not to reflect intracellular Ca2+ diffusion or extracellular diffusion of ACPD and were always accompanied by small outward membrane currents. 3. Repetitive application of ACPD failed to trigger further Ca2+ release. We found that a threshold level of voltage-gated Ca2+ entry during trains of action potentials was needed to prime further mGlu-stimulated Ca2+ release. In contrast, the passage of time alone did not cause the mGlu-release system to reactivate--restoration of ACPD-stimulated Ca2+ release. The spike-mediated Ca2+ signal was unaffected by mGlu-stimulated depletion of intracellular stores. 4. These experiments demonstrate that specific mGlu receptor activation can mobilize Ca2+ in dendrites of CA1 neurons and trigger waves of Ca(2+)-induced Ca(2+)-release throughout the cell. A use-dependent relationship between voltage-gated Ca2+ entry during trains of action potentials and mGlu-stimulated Ca2+ release is suggested.

Effects of metabotropic glutamate receptor antagonists on a rat model of maximum electroshock

2021 ◽  
Vol 29 (2) ◽  
pp. 193-200
Author(s):  
Valentina G. Bashkatova ◽  
Sergey K. Sudakov
Keyword(s):  
Metabotropic Glutamate Receptor ◽  
Thiobarbituric Acid ◽  
Secondary Products ◽  
Receptor Antagonists ◽  
Metabotropic Receptor ◽  
Mglu Receptor ◽  
Metabotropic Glutamate ◽  
Male Wistar Rats ◽  
Convulsive Seizures ◽  
The Brain

AIM: This study aimed to investigate the effect of metabotropic glutamate (mGlu) receptor antagonists on the development of seizure caused by maximum electric shock (MES) and the content of lipid peroxidation (LPO) products in the brain of rats. MATERIALS AND METHODS: Experiments were carried out on male Wistar rats (n = 87) with a mass of 180210 g. In this work, MES was administered. Selective antagonists of I and V subtype mGlu receptors were administered 1 h before MES was administered. Control rats were injected an equivalent amount of saline. The intensity of LPO processes was assessed in terms of the level of secondary products reacting with thiobarbituric acid via a spectrophotometric method. RESULTS: MES led to the development of pronounced clonictonic seizures and increased the level of LPO products in the cerebral cortex of rats by more than threefold. A selective antagonist of subtype V mGlu receptors almost completely stopped the tonic phase of rat seizures and largely prevented the intensification of LPO processes caused by MES. Tonic convulsions were observed in 44% of the experimental animals after the administration of a selective subtype I mGlu receptor antagonist. This antagonist also partially reduced the content of LPO products caused by the effect of MES. CONCLUSION: Thus, mGlu receptors are involved in the development of MES-induced seizures in rats. The most pronounced weakening of convulsive manifestations and the prevention of an increase in the level of LPO products caused by MES were observed in the block of subtype V mGlu receptors. The obtained data confirmed the possibility of using subtype V metabotropic receptor antagonists as anticonvulsants for the treatment of epilepsy with generalized convulsive seizures.

Localization and function of group III metabotropic glutamate receptors in rat pancreatic islets

2002 ◽  
Vol 282 (6) ◽  
pp. E1324-E1333 ◽  
Author(s):  
Qingchun Tong ◽  
Raogo Ouedraogo ◽  
Annette L. Kirchgessner
Keyword(s):  
Pancreatic Islets ◽  
Glutamate Receptors ◽  
Metabotropic Glutamate Receptors ◽  
Secretory Granules ◽  
Glutamate Release ◽  
Receptor Subtype ◽  
Group Iii ◽  
Mglu Receptor ◽  
Receptor Agonists ◽  
Metabotropic Glutamate

Pancreatic islets contain ionotropic glutamate receptors that can modulate hormone secretion. The purpose of this study was to determine whether islets express functional group III metabotropic glutamate (mGlu) receptors. RT-PCR analysis showed that rat islets express the mGlu8 receptor subtype. mGlu8 receptor immunoreactivity was primarily displayed by glucagon-secreting α-cells and intrapancreatic neurons. By demonstrating the immunoreactivities of both glutamate and the vesicular glutamate transporter 2 (VGLUT2) in these cells, we established that α-cells express a glutamatergic phenotype. VGLUT2 was concentrated in the secretory granules of islet cells, suggesting that glutamate might play a role in the regulation of glucagon processing. The expression of mGlu8 by glutamatergic cells also suggests that mGlu8 may function as an autoreceptor to regulate glutamate release. Pancreatic group III mGlu receptors are functional because mGlu8 receptor agonists inhibited glucagon release and forskolin-induced accumulation of cAMP in isolated islets, and (R,S)-cyclopropyl-4-phosphonophenylglycine, a group III mGlu receptor antagonist, reduced these effects. Because excess glucagon secretion causes postprandial hyperglycemia in patients with type 2 diabetes, group III mGlu receptor agonists could be of value in the treatment of these patients.

scholarly journals Metabotropic glutamate receptors in GtoPdb v.2021.3

2021 ◽  
Vol 2021 (3) ◽  
Author(s):  
Francine Acher ◽  
Giuseppe Battaglia ◽  
Hans Bräuner-Osborne ◽  
P. Jeffrey Conn ◽  
Robert Duvoisin ◽  
...  
Keyword(s):  
Glutamate Receptors ◽  
G Protein ◽  
Metabotropic Glutamate Receptors ◽  
Receptor Subtypes ◽  
Allosteric Modulators ◽  
Group Iii ◽  
Mglu Receptor ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Group Ii

Metabotropic glutamate (mGlu) receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Metabotropic Glutamate Receptors [347]) are a family of G protein-coupled receptors activated by the neurotransmitter glutamate [138]. The mGlu family is composed of eight members (named mGlu1 to mGlu8) which are divided in three groups based on similarities of agonist pharmacology, primary sequence and G protein coupling to effector: Group-I (mGlu1 and mGlu5), Group-II (mGlu2 and mGlu3) and Group-III (mGlu4, mGlu6, mGlu7 and mGlu8) (see Further reading).Structurally, mGlu are composed of three juxtaposed domains: a core G protein-activating seven-transmembrane domain (TM), common to all GPCRs, is linked via a rigid cysteine-rich domain (CRD) to the Venus Flytrap domain (VFTD), a large bi-lobed extracellular domain where glutamate binds. mGlu form constitutive dimers, cross-linked by a disulfide bridge. The structures of the VFTD of mGlu1, mGlu2, mGlu3, mGlu5 and mGlu7 have been solved [198, 271, 264, 399]. The structure of the 7 transmembrane (TM) domains of both mGlu1 and mGlu5 have been solved, and confirm a general helical organization similar to that of other GPCRs, although the helices appear more compacted [87, 429, 61]. Recent advances in cryo-electron microscopy have provided structures of full-length mGlu receptor dimers [189]. Studies have revealed the possible formation of heterodimers between either group-I receptors, or within and between group-II and -III receptors [88]. First well characterized in transfected cells, co-localization and specific pharmacological properties also suggest the existence of such heterodimers in the brain [266].[436, 143, 279]. Beyond heteromerization with other mGlu receptor subtypes, increasing evidence suggests mGlu receptors form heteromers and larger order complexes with class A GPCRs (reviewed in [138]). The endogenous ligands of mGlu are L-glutamic acid, L-serine-O-phosphate, N-acetylaspartylglutamate (NAAG) and L-cysteine sulphinic acid. Group-I mGlu receptors may be activated by 3,5-DHPG and (S)-3HPG [30] and antagonized by (S)-hexylhomoibotenic acid [232]. Group-II mGlu receptors may be activated by LY389795 [265], LY379268 [265], eglumegad [350, 430], DCG-IV and (2R,3R)-APDC [351], and antagonised by eGlu [168] and LY307452 [421, 103]. Group-III mGlu receptors may be activated by L-AP4 and (R,S)-4-PPG [128]. An example of an antagonist selective for mGlu receptors is LY341495, which blocks mGlu2 and mGlu3 at low nanomolar concentrations, mGlu8 at high nanomolar concentrations, and mGlu4, mGlu5, and mGlu7 in the micromolar range [183]. In addition to orthosteric ligands that directly interact with the glutamate recognition site, allosteric modulators that bind within the TM domain have been described. Negative allosteric modulators are listed separately. The positive allosteric modulators most often act as ‘potentiators’ of an orthosteric agonist response, without significantly activating the receptor in the absence of agonist.

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