Actions of phenylglycine analogs at subtypes of the metabotropic glutamate receptor family

Abstract

The functional effects of phenylglycine analogs on metabotropic glutamate receptor (mGluR) subtypes mGluR 1α, mGluR 2 and mGluR 4 were examined. ( S)-4-Carboxyphenylglycine (IC 50 = 65 ± 5 μM), ( R, S)- α-methyl-4-carboxyphenylglycine(IC 50 = 155 ± 38 μM) and ( S)-3-carboxy-4-hydroxyphenylglycine (IC 50 = 290 ± 47 μM) competitively antagonized glutamate-stimulated phosphoinositide hydrolysis in baby hamster kidney (BHK) cells stably expressing mGluR 1α. ( S)-4-Carboxyphenylglycine and ( R, S)- α-methyl-4-carboxyphenylglycine competitively antagonized glutamate-induced inhibition of forskolin-stimulated cAMP-formation in BHK cells stably expressing mGluR 2 with IC 50 values of 577 ± 74 μM and 340 ± 59 μM, respectively. ( R, S)-4-carboxy-3-hydroxyphenylglycine( R)-3-hydroxyphenylglycine and ( S)-3-carboxy-4-hydroxyphenylglycine were agonists at mGluR 2 with EC 50 values of 48 ± 5 μM, 451 ± 93 and 97 ± 12 μM, respectively. In parallel experiments, no activities of these phenylglycine analogs at mGluR 4 were observed. The present report demonstrates that phenylglycine analogs possess differential functional activities at subtypes of the mGluR family.