Phenylglycine derivatives discriminate between mGluR1- and mGluR5-mediated responses

doi:10.1016/0028-3908(95)00079-L

Neuropharmacology

Volume 34, Issue 8, August 1995, Pages 895-903

https://doi.org/10.1016/0028-3908(95)00079-L Get rights and content

Abstract

The effects of the phenylglycine derivatives, α-methyl-4-carboxyphenylglycine (MCPG), 4-carboxyphenylglycine (4CPG), 4-carboxy-3-hydroxyphenylglycine (4C3HPG), 3-hydroxyphenylglycine (3HPG) and 3,5-dihydrohyphenylglycine (DHPG) were tested on LLC-PK1 cells transiently expressing the rat mGluR1a or mGluR5a receptors. As previously reported by others, (S)-3HPG and (RS)-DHPG were found to be partial agonists at mGluR1a, whereas (+)-MCPG, (S)-4CPG and (S)-4C3HPG competitively antagonized the effect of Glu. Surprisingly, the 4-carboxy derivatives of phenylglycine antagonized the effect of 1S,3R-ACPD on mGluR1a with lower K_B values. On mGluR5a, (S)-3HPG and (RS)-DHPG are also partial agonists. However, in contrast to their effects on mGluR1a, (S)-4CPG did not inhibit the effect of Glu or 1S,3R-ACPD, and (S)-4C3HPG acted as an agonist at high concentration. Whereas no significant antagonism of the Glu effect on mGluR5a was observed with 1 mM (+)-MCPG, this compound was found to potently and competitively antagonize the effect of 1S,3R-ACPD. Finally, the effect of 4CPG was also examined on cultured cortical and cerebellar neurons that express mGluR5 and mGluR1 mRNA, respectively. 4CPG inhibited 1S,3R-ACPD-stimulated IP production in cerebellar neurons only. These results (1) demonstrate that phenylglycine derivatives can be used to discriminate between effects mediated by mGluR1 and mGluR5 and (2) suggest that the apparent potency of phenylglycine antagonists depends on the agonist used to activate these receptors.

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General paperPhenylglycine derivatives discriminate between mGluR1- and mGluR5-mediated responses

Abstract

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(RS)-α-Methyl-4-carboxyphenylglycine neither prevents induction of LTP nor antagonizes metabotropic glutamate receptors in CA1 hippocampal neurons

J. Neurophysiol.

General paper
Phenylglycine derivatives discriminate between mGluR1- and mGluR5-mediated responses