A PHARMACOLOGICAL CHARACTERIZATION OF THE MGLUR1-ALPHA SUBTYPE OF THE METABOTROPIC GLUTAMATE-RECEPTOR EXPRESSED IN A CLONED BABY HAMSTER-KIDNEY CELL-LINE

The pharmacological specificity of the mGluR1alpha subtype of the metabotropic glutamate receptor (mGluR) was examined in a cloned baby hamster kidney cell line (BHK-ts13) measuring [H-3]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 [H-3]glutamate on membranes prepared from BHK-ts13 cells expressing the mGluR1alpha subtype showed that glutamate binds to a single affinity state of this receptor with a limited capacity (K(d) = 296 nM, B(max) = 0.8 pmol/mg protein). In competition experiments, [H-3]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.