Antagonism of presynaptically mediated depressant responses and cyclic AMP-coupled metabotropic glutamate receptors.

The depression of monosynaptic excitation of neonatal rat motoneurones by (1S,3S)- and (1S,3R)-1-aminocyclopentane-1,3-dicarboxylate (ACPD) and by L-2-amino-4-phosphonobutyrate (L-AP4), which is probably presynaptically mediated, is antagonized by (+/-)- and (+)-alpha-methyl-4-carboxyphenylglycine (MCPG). The same phenylglycine derivatives also antagonize the depression of forskolin-stimulated cyclic AMP synthesis effected by the two ACPD stereoisomers and by L-AP4. These results support previous suggestions that presynaptic depression is mediated by metabotropic glutamate receptors negatively coupled to adenylyl cyclase activity. MCPG is the first antagonist to be reported for these receptors.