Article date: 1993/8/13
PubMed ID: 7690672
Journal name: Brain research (ISSN: 0006-8993)
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.
Author List: Thomsen C, Mulvihill E R, Haldeman B, Pickering D S, Hampson D R, Suzdak P D
Publication Types: Journal Article; Research Support, Non-U.S. Gov't
Substances mentioned in the article: Amino Acids, Diamino; Aminobutyrates; Glutamates; Inositol Phosphates; Neurotoxins; Quinoxalines; Receptors, Glutamate; Recombinant Proteins; Virulence Factors, Bordetella; beta-N-methylamino-L-alanine; 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; Ibotenic Acid; Glutamic Acid; Dizocilpine Maleate; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Quisqualic Acid; Pertussis Toxin; 2-amino-4-phosphonobutyric acid;
Mesh terms: Amino Acids, Diamino/pharmacology; Aminobutyrates/pharmacology; Animals; Binding, Competitive; Cell Line; Cell Membrane/metabolism; Clone Cells; Cricetinae; Dizocilpine Maleate/pharmacology; Glutamates/metabolism; Glutamic Acid; Ibotenic Acid/analogs & derivatives; Inositol Phosphates/metabolism; Kidney; Kinetics; Neurotoxins/pharmacology; Pertussis Toxin; Quinoxalines/pharmacology; Quisqualic Acid/pharmacology; Receptors, Glutamate/biosynthesis; Recombinant Proteins/biosynthesis; Transfection; Virulence Factors, Bordetella/pharmacology; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;