title: 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 mGluR1 alpha, mGluR2 and mGluR4 were examined. (S)-4-Carboxyphenylglycine (IC50 = 65 +/- 5 microM), (R,S)-alpha-methyl-4-carboxyphenylglycine (IC50 = 155 +/- 38 microM) and (S)-3-carboxy-4-hydroxyphenylglycine (IC50 = 290 +/- 47 microM) competitively antagonized glutamate-stimulated phosphoinositide hydrolysis in baby hamster kidney (BHK) cells stably expressing mGluR1 alpha. (S)-4-Carboxyphenylglycine and (R,S)-alpha-methyl-4-carboxyphenylglycine competitively antagonized glutamate-induced inhibition of forskolin-stimulated cAMP-formation in BHK cells stably expressing mGluR2 with IC50 values of 577 +/- 74 microM and 340 +/- 59 microM, respectively. (R,S)-4-carboxy-3-hydroxyphenylglycine, (R)-3-hydroxyphenylglycine and (S)-3-carboxy-4-hydroxyphenylglycine were agonists at mGluR2 with EC50 values of 48 +/- 5 microM, 451 +/- 93 and 97 +/- 12 microM, respectively. In parallel experiments, no activities of these phenylglycine analogs at mGluR4 were observed. The present report demonstrates that phenylglycine analogs possess differential functional activities at subtypes of the mGluR family.
authors.affiliation: Novo Nordisk A/S, Department of Receptor Neurochemistry, Måløv, Denmark.
authors.forename: C
authors.initials: C
authors.lastname: Thomsen
authors.forename: E
authors.initials: E
authors.lastname: Boel
authors.forename: P D
authors.initials: PD
authors.lastname: Suzdak
mesh_terms: D000818:Animals; D001667:Binding, Competitive; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects; D006224:Cricetinae; D000242:Cyclic AMP / Q000096:biosynthesis; D005998:Glycine / Q000031:analogs & derivatives*; D006868:Hydrolysis; D007608:Kainic Acid / Q000378:metabolism / Q000494:pharmacology; D007668:Kidney / Q000166:cytology; D008297:Male; D016202:N-Methylaspartate / Q000378:metabolism / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects* / Q000378:metabolism; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism / Q000494:pharmacology
chemical_list: D010716:Phosphatidylinositols; D018094:Receptors, Metabotropic Glutamate; D016202:N-Methylaspartate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D000242:Cyclic AMP; D007608:Kainic Acid; D005998:Glycine