Actions of phenylglycine analogs at subtypes of the metabotropic glutamate receptor family.
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.
Thomsen
C
C
Novo Nordisk A/S, Department of Receptor Neurochemistry, Måløv, Denmark.
Boel
E
E
Suzdak
P D
PD
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
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