A pharmacological characterization of the mGluR1 alpha subtype of the metabotropic glutamate receptor expressed in a cloned baby hamster kidney cell line

Brain Res. 1993 Aug 13;619(1-2):22-8. doi: 10.1016/0006-8993(93)91592-g.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids, Diamino / pharmacology
  • Aminobutyrates / pharmacology
  • Animals
  • Binding, Competitive
  • Cell Line
  • Cell Membrane / metabolism
  • Clone Cells
  • Cricetinae
  • Dizocilpine Maleate / pharmacology
  • Glutamates / metabolism*
  • Glutamates / pharmacology
  • Glutamic Acid
  • Ibotenic Acid / analogs & derivatives
  • Ibotenic Acid / pharmacology
  • Inositol Phosphates / metabolism*
  • Kidney
  • Kinetics
  • Neurotoxins / pharmacology
  • Pertussis Toxin
  • Quinoxalines / pharmacology
  • Quisqualic Acid / pharmacology
  • Receptors, Glutamate / biosynthesis
  • Receptors, Glutamate / classification
  • Receptors, Glutamate / metabolism*
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / metabolism
  • Transfection
  • Virulence Factors, Bordetella / pharmacology
  • alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid

Substances

  • 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