INVOLVEMENT OF A CYCLIC-AMP PATHWAY IN GROUP-I METABOTROPIC GLUTAMATE-RECEPTOR RESPONSES IN NEONATAL RAT CORTEX

3,5-dihydroxyphenylglycine (DHPG), (S)-3-hydroxyphenylglycine and (S)- 4-carboxy-3-hydroxyphenylglycine (S-4C3HPG) stimulated phosphoinositid e hydrolysis in neonatal rat cortical slices, but with lower maximal e ffect, in comparison with 2S,1'S,2'S-2-(2'-carboxycyclopropyl)glycine (L-CCG I) or (1S,3R)-1-aminocyclo-pentane-1,3-dicarboxylic acid (1S,3R -ACPD). DHPG, 1S,3R-ACPD, and S-4C3HPG also evoked a rapidly desensiti zing increase in [Ca2+](i) in cortical layers of neonatal brain slices . (R,S)-alpha-methyl-4-tetrazolylphenylglycine (MTPG), and (R,S)-alpha -methyl-4-phosphono-phenylglycine (MPPG) inhibited the increase of pho sphoinositide hydrolysis elicited by 1S,3R-ACPD but not that by R,S-DH PG. In contrast, the selective group II receptor agonist )-2-amino-bic yclo-[3.1.0]-hexane-2,6-dicarboxylate (LY 354740) potentiated the resp onse of R,S-DHPG. Finally, 8-(4-chlorophenylthio)-cAMP, a membrane per meant analogue of cAMP, reversed the stimulatory effect of 1S,3R-ACPD and S-4C3HPG on phosphoinositide hydrolysis and [Ca2+](i) mobilization , without affecting the response induced by R,S-DHPG. These data sugge st that, in neonatal rat cortex, the activation of group II metabotrop ic glutamate receptors potentiates the phosphoinositide hydrolysis and [Ca2+](i) responses mediated by group I metabotropic glutamate recept ors. (C) 1997 Elsevier Science B.V.