ACTIONS OF PHENYLGLYCINE ANALOGS AT SUBTYPES OF THE METABOTROPIC GLUTAMATE-RECEPTOR FAMILY

The functional effects of phenylglycine analogs on metabotropic glutam ate receptor (mGluR) subtypes mGluR1alpha, mGluR2 and mGluR4 were exam ined. (S)-4-Carboxyphenylglycine (IC50 = 65 +/- 5 muM), (PS)-alpha-met hyl-4-carboxyphenylglycine (IC50 = 155 +/- 38 muM) and (S)-3-carboxy-4 -hydroxyphenylglycine (IC50 = 290 +/- 47 AM) competitively antagonized glutamate-stimulated phosphoinositide hydrolysis in baby hamster kidn ey (BHK) cells stably expressing mGluRa1alpha. (S)-4-Carboxyphenylglyc ine and (R,S)-alpha-methyl-4-carboxyphenylglycine competitively antago nized glutamate-induced inhibition of forskolin-stimulated cAMP-format ion in BHK cells stably expressing mGluR2 With IC50 values of 577 +/- 74 muM and 340 +/- 59 muM, respectively. (PS)-4-carboxy-3-hydroxypheny lglycine, (R)-3-hydroxyphenylglycine and (S)-3-carboxy-4-hydroxyphenyl glycine were agonists at mGluR2 with EC50 values of 48 +/- 5 muM, 451 +/- 93 and 97 +/- 12 muM, respectively. In parallel experiments, no ac tivities of these phenylglycine analogs at mGluR4 were observed. The p resent report demonstrates that phenylglycine analogs possess differen tial functional activities at subtypes of the mGluR family.