I. Brabet et al., PHENYLGLYCINE DERIVATIVES DISCRIMINATE BETWEEN MGLUR1-MEDIATED AND MGLUR5-MEDIATED RESPONSES, Neuropharmacology, 34(8), 1995, pp. 895-903
The effects of the phenylglycine derivatives, alpha-methyl-4-carboxyph
enylglycine (MCPG), 4-carboxyphenylglycine (4CPG), 4-carboxy-3-hydroxy
phenylglycine (4C3HPG), 3-hydroxyphenylglycine (3HPG) and 3,4-dihydroh
yphenylglycine (DHPG) were tested on LLC-PK1 cells transiently express
ing the rat mGluRla or mGluR5a receptors. As previously reported by ot
hers, (S)-3HPG and (RS)-DHPG were found to be partial agonists at mGlu
R la, whereas (+)-MCPG, (S)-4CPG and (S)-4C3HPG competitively antagoni
zed the effect of Glu. Surprisingly, the 4-carboxy derivatives of phen
ylglycine antagonized the effect of 1S,3R-ACPD on mGluR1a with lower K
-B values. On mGluRSa, (S)-3HPG and (RS)-DHPG are also partial agonist
s. 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 ag
onist at high concentration. Whereas no significant antagonism of the
Glu effect on mGluRSa was observed with 1 mM(+)-MCPG, this compound wa
s found to potently and competitively antagonize the effect of 1S,3R-A
CPD. Finally, the effect of 4CPG was also examined on cultured cortica
l and cerebellar neurons that express mGluR5 and mGluR1 mRNA, respecti
vely. 4CPG inhibited 1S,3R-ACPD stimulated IP production in cerebellar
neurons only. These results (1) demonstrate that phenylglycine deriva
tives can be used to discriminate between effects mediated by mGluR1 a
nd mGluR5 and (2) suggest that the apparent potency of phenylglycine a
ntagonists depends on the agonist used to activate these receptors.