A Novel Binding Assay For Metabotropic Glutamate Receptors Using [3H] ʟ-Quisqualic Acid And Recombinant Receptors

  title={A Novel Binding Assay For Metabotropic Glutamate Receptors Using [3H] ʟ-Quisqualic Acid And Recombinant Receptors},
  author={Hiroshi Ohashi and Takaharu Maruyama and Hidemi Higashi-Matsumoto and Takashi Nomoto and Yutaka Takeuchi},
  journal={Zeitschrift f{\"u}r Naturforschung C},
  pages={348 - 355}
We established a methodology to analyze radioligand binding to the recombinant type 1a metabotropic glutamate receptor (mGluR1a). A full-length ᴄDNA encoding mGluR1a, which was isolated from a λ gt 11 ᴄDNA library of human cerebellar origin, was expressed in a baculovirus/Sf9 insect cell system. Membrane fractions with recombinant receptor expression were analyzed for the binding of [3H]L-quisqualic acid (ʟ-QA), which is known to be a potent agonist of mGluR1a. Efficient binding of the… Expand
Correlation of receptor occupancy of metabotropic glutamate receptor subtype 1 (mGluR1) in mouse brain with in vivo activity of allosteric mGluR1 antagonists.
The relationship between receptor occupancy and in vivo pharmacological activity of mGluR1 antagonists was clarified and receptor occupancy assays could help provide guidelines for selecting appropriate doses of allosteric mGLUR1 antagonist for examining the function of mR1 in vivo. Expand
In Vitro Pharmacological Characterization of Novel Isoxazolopyridone Derivatives as Allosteric Metabotropic Glutamate Receptor 7 Antagonists
MMPIP is the first allosteric mGluR7-selective antagonist that could potentially be useful as a pharmacological tool for elucidating the roles of mGLUR7 on central nervous system functions. Expand
Identification of a novel transmembrane domain involved in the negative modulation of mGluR1 using a newly discovered allosteric mGluR1 antagonist, 3-cyclohexyl-5-fluoro-6-methyl-7-(2-morpholin-4-ylethoxy)-4H-chromen-4-one
Results indicate that some mGluR1 allosteric antagonists require N760 in TM5 to demonstrate negative modulation of mGlutamate-induced intracellular Ca(2+) mobilization in addition to the reported amino acid residues in TM6 and TM7. Expand
Unique Antipsychotic Activities of the Selective Metabotropic Glutamate Receptor 1 Allosteric Antagonist 2-Cyclopropyl-5-[1-(2-fluoro-3-pyridinyl)-5-methyl-1H-1,2,3-triazol-4-yl]-2,3-dihydro-1H-isoindol-1-one
The results suggest that the antipsychotic activities of mGluR1 antagonists are more similar to those of atypical antipsychotics than those of typical antippsychotics. Expand
Pharmacological Characterization of a New, Orally Active and Potent Allosteric Metabotropic Glutamate Receptor 1 Antagonist, 4-[1-(2-Fluoropyridin-3-yl)-5-methyl-1H-1,2,3-triazol-4-yl]-N-isopropyl-N-methyl-3,6-dihydropyridine-1(2H)-carboxamide (FTIDC)
FTIDC is a highly potent and selective allosteric mGluR1 antagonist and a compound having oral activity without species differences in its antagonistic activity on recombinant human, mouse, and rat mGlamR1 and could be a valuable tool for elucidating the functions of mGLUR1 not only in rodents but also in humans. Expand
A Review of Glutamate Receptors II: Pathophysiology and Pathology
The diseases in which the pathophysiology and pathology are associated, in part, with the glutamate system are explored, including epilepsy, amnesia, anxiety, hyperalgesia and psychosis. Expand
Isoxazolopyridone derivatives as allosteric metabotropic glutamate receptor 7 antagonists.
This Letter describes the synthesis and evaluation of mGluR7 antagonists in the isoxazolopyridone series, finding that 2 showed good oral bioavailability and brain penetrability, suggesting that 2 may be useful for in vivo study to elucidate the role of mR7. Expand
Progress toward advanced understanding of metabotropic glutamate receptors: structure, signaling and therapeutic indications.
The metabotropic glutamate (mGlu) receptors are a group of Class C seven-transmembrane spanning/G protein-coupled receptors (7TMRs/GPCRs). These receptors are activated by glutamate, one of theExpand
Sf9 cells: a versatile model system to investigate the pharmacological properties of G protein-coupled receptors.
Sf9 cells are a versatile model system to investigate the pharmacological properties of GPCRs and can be employed for ligand screening in medicinal chemistry programs, using radioligand binding assays or functional assays, like the steady-state GTPase- or [(35)S]GTPγS binding assay. Expand
Metabotropic Glutamate Receptors 1 Regulates Rat Carotid Body Response to Acute Hypoxia via Presynaptic Mechanism
Background: The carotid body (CB) plays a critical role in oxygen sensing; however, the role of glutamatergic signaling in the CB response to hypoxia remains uncertain. We previously found thatExpand


Sequence and expression of a metabotropic glutamate receptor
The complementary DNA of a metabotropic glutamate receptor coupled to inositol phosphate/Ca2+ signal transduction has been cloned and characterized and abundant expression of this messenger RNA is observed in neuronal cells in hippocampal dentate gyrus and CA2−3 and in Cerebellar Purkinje cells, suggesting the importance of this receptor in specific hippocampal and cerebellar functions. Expand
The metabotropic glutamate receptors: Structure and functions
Recently, glutamate has been shown to regulate ion channels and enzymes producing second messengers via specific receptors coupled to G-proteins, and the existence of these receptors is changing views on the functioning of fast excitatory synapses. Expand
What is molecular diversity?
This book addresses generation of molecular diversity, application of diversity for screening against alternative targets of all types, analysis of results and their application in various scientific disciplines. Expand
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