Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
???displayArticle.abstract???
Metabotropic glutamate receptors (mGluRs) are membrane receptors that play a central role in the modulation of synaptic transmission and neuronal excitability and whose dysregulation is implicated in diverse neurological disorders. Most current understanding about the electrophysiological properties of such receptors has been determined using recombinant proteins. However, recombinant receptors do not necessarily recapitulate the properties of native receptors due to the lack of obligated accessory proteins, some of which are differentially expressed as function of developmental stage and brain region. To overcome this limitation, we sought to microtransplant entire synaptosome membranes from frozen rat cortex into Xenopus oocytes, and directly analyze the responses elicited by native mGluRs. We recorded ion currents elicited by 1 mM glutamate using two electrodes voltage clamp. Glutamate produced a fast ionotropic response (6 ± 0.3 nA) in all microtransplanted oocytes (n = 218 oocytes) and a delayed oscillatory response (52 ± 7 nA) in 73% of them. The participation of Group 1 mGluRs was confirmed by the presence of metabotropic oscillations during the administration of (±)-1-Aminocyclopentane-trans-1,3-dicarboxylic acid (ACPD; Group 1 mGluR agonist), and the absence of oscillations during co-administration of N-(1-adamantyl)quinoxaline-2-carboxamide (NPS 2390; Group 1 mGluR antagonist). Since both mGluR1 and mGluR5 belong to Group 1 mGluRs, further investigation revealed that mGluR1 antagonism with LY 456236 has little effect on metabotropic oscillations, while mGluR5 antagonism with 100 µM AZD 9272 has significant reduction of metabotropic currents elicited by ACPD and glutamate. We confirmed the expression of mGluR1 and mGluR5 in native synaptosomes by immunoblots, both of which are enhanced when compared to their counterpart proteins in rat cortex tissue lysates. Finally, these results demonstrate the merit of using microtransplantation of native synaptosomes for the study of mGluRs and the contribution of mGluR5 to the metabotropic glutamate signaling, providing a better tool for the understanding of the role of these receptors in neurological disorders.
Albasanz,
Impaired metabotropic glutamate receptor/phospholipase C signaling pathway in the cerebral cortex in Alzheimer's disease and dementia with Lewy bodies correlates with stage of Alzheimer's-disease-related changes.
2005, Pubmed
Albasanz,
Impaired metabotropic glutamate receptor/phospholipase C signaling pathway in the cerebral cortex in Alzheimer's disease and dementia with Lewy bodies correlates with stage of Alzheimer's-disease-related changes.
2005,
Pubmed
Bernareggi,
Properties of glutamate receptors of Alzheimer's disease brain transplanted to frog oocytes.
2007,
Pubmed
Caraci,
Metabotropic glutamate receptors: the potential for therapeutic applications in Alzheimer's disease.
2018,
Pubmed
Crupi,
Role of Metabotropic Glutamate Receptors in Neurological Disorders.
2019,
Pubmed
DeLisle,
Effect of inositol trisphosphate and calcium on oscillating elevations of intracellular calcium in Xenopus oocytes.
1990,
Pubmed
,
Xenbase
DeLong,
Basal Ganglia Circuits as Targets for Neuromodulation in Parkinson Disease.
2015,
Pubmed
Enz,
Metabotropic glutamate receptors and interacting proteins: evolving drug targets.
2012,
Pubmed
Eusebi,
Microtransplantation of ligand-gated receptor-channels from fresh or frozen nervous tissue into Xenopus oocytes: a potent tool for expanding functional information.
2009,
Pubmed
,
Xenbase
Flint,
Endogenous activation of metabotropic glutamate receptors in neocortical development causes neuronal calcium oscillations.
1999,
Pubmed
Giuffrida,
A reduced number of metabotropic glutamate subtype 5 receptors are associated with constitutive homer proteins in a mouse model of fragile X syndrome.
2005,
Pubmed
Grewer,
Glutamate forward and reverse transport: from molecular mechanism to transporter-mediated release after ischemia.
2008,
Pubmed
Grueter,
Group II and III metabotropic glutamate receptors suppress excitatory synaptic transmission in the dorsolateral bed nucleus of the stria terminalis.
2005,
Pubmed
Gulyássy,
Proteomic comparison of different synaptosome preparation procedures.
2020,
Pubmed
Hamilton,
Metabotropic glutamate receptor 5 knockout reduces cognitive impairment and pathogenesis in a mouse model of Alzheimer's disease.
2014,
Pubmed
Hamilton,
Chronic Pharmacological mGluR5 Inhibition Prevents Cognitive Impairment and Reduces Pathogenesis in an Alzheimer Disease Mouse Model.
2016,
Pubmed
Hansen,
Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels.
2021,
Pubmed
Ishibashi,
Unchanged type 1 metabotropic glutamate receptor availability in patients with Alzheimer's disease: A study using 11C-ITMM positron emission tomography.
2019,
Pubmed
Ivorra,
Functional transplantation of chloride channels from the human syncytiotrophoblast microvillous membrane to Xenopus oocytes.
2002,
Pubmed
,
Xenbase
Jin,
Phosphorylation and feedback regulation of metabotropic glutamate receptor 1 by calcium/calmodulin-dependent protein kinase II.
2013,
Pubmed
Jin,
Selective increases of AMPA, NMDA, and kainate receptor subunit mRNAs in the hippocampus and orbitofrontal cortex but not in prefrontal cortex of human alcoholics.
2014,
Pubmed
Lauterborn,
Increased excitatory to inhibitory synaptic ratio in parietal cortex samples from individuals with Alzheimer's disease.
2021,
Pubmed
Limon,
Loss of functional GABA(A) receptors in the Alzheimer diseased brain.
2012,
Pubmed
,
Xenbase
Madeira,
Elevated Glutamate and Glutamine Levels in the Cerebrospinal Fluid of Patients With Probable Alzheimer's Disease and Depression.
2018,
Pubmed
Mao,
Group I Metabotropic Glutamate Receptors and Interacting Partners: An Update.
2022,
Pubmed
Marsal,
Incorporation of acetylcholine receptors and Cl- channels in Xenopus oocytes injected with Torpedo electroplaque membranes.
1995,
Pubmed
,
Xenbase
Mazzo,
Reconstitution of synaptic Ion channels from rodent and human brain in Xenopus oocytes: a biochemical and electrophysiological characterization.
2016,
Pubmed
,
Xenbase
Menuz,
TARP auxiliary subunits switch AMPA receptor antagonists into partial agonists.
2007,
Pubmed
Miller,
Microtransplantation of Synaptic Membranes to Reactivate Human Synaptic Receptors for Functional Studies.
2022,
Pubmed
,
Xenbase
Murenzi,
Evaluation of microtransplantation of rat brain neurolemma into Xenopus laevis oocytes as a technique to study the effect of neurotoxicants on endogenous voltage-sensitive ion channels.
2017,
Pubmed
,
Xenbase
Nedergaard,
Beyond the role of glutamate as a neurotransmitter.
2002,
Pubmed
Niswender,
Metabotropic glutamate receptors: physiology, pharmacology, and disease.
2010,
Pubmed
Nitsch,
Metabotropic glutamate receptor subtype mGluR1alpha stimulates the secretion of the amyloid beta-protein precursor ectodomain.
1997,
Pubmed
Ostapchenko,
Increased prion protein processing and expression of metabotropic glutamate receptor 1 in a mouse model of Alzheimer's disease.
2013,
Pubmed
Palma,
Microtransplantation of membranes from cultured cells to Xenopus oocytes: a method to study neurotransmitter receptors embedded in native lipids.
2003,
Pubmed
,
Xenbase
Paquet,
The PDZ scaffold NHERF-2 interacts with mGluR5 and regulates receptor activity.
2006,
Pubmed
Parker,
Localized all-or-none calcium liberation by inositol trisphosphate.
1990,
Pubmed
,
Xenbase
Piers,
Translational Concepts of mGluR5 in Synaptic Diseases of the Brain.
2012,
Pubmed
Platt,
The role of glutamate in central nervous system health and disease--a review.
2007,
Pubmed
Putney,
Type 3 inositol 1,4,5-trisphosphate receptor and capacitative calcium entry.
1997,
Pubmed
,
Xenbase
Reiner,
Glutamatergic Signaling in the Central Nervous System: Ionotropic and Metabotropic Receptors in Concert.
2018,
Pubmed
Ronesi,
Disrupted Homer scaffolds mediate abnormal mGluR5 function in a mouse model of fragile X syndrome.
2012,
Pubmed
Rousset,
Mammalian Brain Ca2+ Channel Activity Transplanted into Xenopus laevis Oocytes.
2022,
Pubmed
,
Xenbase
Ryo,
Expression of the metabotropic glutamate receptor mGluR1 alpha and the ionotropic glutamate receptor GluR1 in the brain during the postnatal development of normal mouse and in the cerebellum from mutant mice.
1993,
Pubmed
Saugstad,
Metabotropic glutamate receptors activate G-protein-coupled inwardly rectifying potassium channels in Xenopus oocytes.
1996,
Pubmed
,
Xenbase
Tu,
Coupling of mGluR/Homer and PSD-95 complexes by the Shank family of postsynaptic density proteins.
1999,
Pubmed
Um,
Metabotropic glutamate receptor 5 is a coreceptor for Alzheimer aβ oligomer bound to cellular prion protein.
2013,
Pubmed
,
Xenbase
Wang,
Role of Glutamate and NMDA Receptors in Alzheimer's Disease.
2017,
Pubmed
Zeppillo,
Functional impairment of cortical AMPA receptors in schizophrenia.
2022,
Pubmed
Zhang,
Gating and modulation of a hetero-octameric AMPA glutamate receptor.
2021,
Pubmed
Zwart,
Microtransplantation of human brain receptors into oocytes to tackle key questions in drug discovery.
2019,
Pubmed
,
Xenbase
