EFFECTS OF BROMOHOMOIBOTENATE ON METABOTROPIC GLUTAMATE RECEPTORS

(S)-BROMOHOMOIBOTENIC acid [(S)-BrHIbo] stereoselectively antagonized glutamate-stimulated phosphoinositide (PI) hydrolysis in baby hamster kidney (BHK) cells expressing mGluR1a in a competitive manner with an IC50 of 250 mu M. However, (S)-BrHIbo did not inhibit (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid [(1S,3R)-ACPD]-induced PI hydrolysis in rat hippocampal slices. (S)- or (R)-BrHIbo did not show any effects on forskolin-stimulated cAMP-formation in BHK cells expressing mGluR2 or mGluR4 but did displace [H-3]2-amino-4-phosphonobutyrate ([H-3]AP4) binding from rat corticalmembranes with high affinities (IC50 = 1.0 mu M and 1.1 mu M, respectively). These data suggest that (S)-BrHIbo may interact with multiple PI-coupled glutamate receptors, however, at concentrations that are several fold higher than for displacement of [H-3]AP4 binding from rat cortical membranes.