title: A pharmacological characterization of the mGluR1 alpha subtype of the metabotropic glutamate receptor expressed in a cloned baby hamster kidney cell line.
abstract: The pharmacological specificity of the mGluR1 alpha subtype of the metabotropic glutamate receptor (mGluR) was examined in a cloned baby hamster kidney cell line (BHK-ts13) measuring [3H]glutamate binding and inositol phosphate (PI) hydrolysis. PI-hydrolysis was maximally stimulated by quisqualate (1112 +/- 105% of basal), glutamate (1061 +/- 70% of basal), ibotenate (1097 +/- 115% of basal) and beta-N-methylamino-L-alanine (BMAA) (1010 +/- 104% of basal). In contrast, the maximal stimulation of PI-hydrolysis by (1S,3R)-1-amino-cyclopentane-1,3-dicarboxylic acid (t-ACPD) was only 673 +/- 78% of the basal level. The relative order of potency was quisqualate > glutamate > ibotenate > t-ACPD > BMAA. Agonist-stimulated PI-hydrolysis was attenuated (25 +/- 4% inhibition) by L-2-amino-3-phosphonopropionic acid and partially blocked (44 +/- 7%) by pertussis toxin treatment. Saturation binding studies with [3H]glutamate on membranes prepared from BHK-ts13 cells expressing the mGluR1 alpha subtype showed that glutamate binds to a single affinity state of this receptor with a limited capacity (Kd = 296 nM, Bmax = 0.8 pmol/mg protein). In competition experiments, [3H]glutamate was displaced by quisqualate, glutamate, ibotenate, t-ACPD and BMAA with a rank order of potency similar to that found for stimulation of PI-hydrolysis.
authors.affiliation: Novo Nordisk A/S, CNS Discovery, Pharmaceuticals Research, Måløv, Denmark.
authors.forename: C
authors.initials: C
authors.lastname: Thomsen
authors.forename: E R
authors.initials: ER
authors.lastname: Mulvihill
authors.forename: B
authors.initials: B
authors.lastname: Haldeman
authors.forename: D S
authors.initials: DS
authors.lastname: Pickering
authors.forename: D R
authors.initials: DR
authors.lastname: Hampson
authors.forename: P D
authors.initials: PD
authors.lastname: Suzdak
mesh_terms: D000599:Amino Acids, Diamino / Q000494:pharmacology; D000613:Aminobutyrates / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002999:Clone Cells; D006224:Cricetinae; D000087522:Cyanobacteria Toxins; D016291:Dizocilpine Maleate / Q000494:pharmacology; D005971:Glutamates / Q000378:metabolism* / Q000494:pharmacology; D018698:Glutamic Acid; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism*; D007668:Kidney; D007700:Kinetics; D009498:Neurotoxins / Q000494:pharmacology; D037342:Pertussis Toxin; D011810:Quinoxalines / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology; D017470:Receptors, Glutamate / Q000096:biosynthesis / Q000145:classification / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D014162:Transfection; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
chemical_list: D000599:Amino Acids, Diamino; D000613:Aminobutyrates; D000087522:Cyanobacteria Toxins; D005971:Glutamates; D007295:Inositol Phosphates; D009498:Neurotoxins; D011810:Quinoxalines; D017470:Receptors, Glutamate; D011994:Recombinant Proteins; D010566:Virulence Factors, Bordetella; C001824:beta-N-methylamino-L-alanine; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D007051:Ibotenic Acid; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D016318:Quisqualic Acid; D037342:Pertussis Toxin; C012729:2-amino-4-phosphonobutyric acid