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AN amino acid, 3,5-dihydroxyphenylglycine (DHPG) induced current responses in Xenopus oocytes expressing a metabotropic glutamate receptor clone mGluRl. Apparent EC50 of DHPG for mGluRl was slightly lower than that of (±)-l-aminocyclopentane-trans-l,3-dicarboxylic acid (ACPD). DHPG responses were partially inhibited by 2-amino-3-phosphonopropionic acid (AP-3). DHPG had no effect on ionotropic glutamate receptors whose expression was induced in the oocytes following injection of poly(A)+ mRNA of rat brains. In hippocampal slices, DHPG produced slow excitation of pyramidal cells, resulting from a depression of Ca2+-dependent K+ current and a voltage-dependent K+ current. These results indicate that DHPG is a specific and potent agonist of mGluRs.