Involvement of a cyclic-AMP pathway in group I metabotropic glutamate receptor responses in neonatal rat cortex

Abstract 3,5-dihydroxyphenylglycine (DHPG), ( S )-3-hydroxyphenylglycine and ( S )-4-carboxy-3-hydroxyphenylglycine ( S -4C3HPG) stimulated phosphoinositide hydrolysis in neonatal rat cortical slices, but with lower maximal effect, in comparison with 2 S ,1′ S ,2′ S -2-(2′-carboxycyclopropyl)glycine ( l -CCG I) or (1 S ,3 R )-1-aminocyclo-pentane-1,3-dicarboxylic acid (1 S ,3 R -ACPD). DHPG, 1 S ,3 R -ACPD, and S -4C3HPG also evoked a rapidly desensitizing increase in [Ca 2+ ] i in cortical layers of neonatal brain slices. ( R , S )- α -methyl-4-tetrazolylphenylglycine (MTPG), and ( R , S )- α -methyl-4-phosphono-phenylglycine (MPPG) inhibited the increase of phosphoinositide hydrolysis elicited by 1 S ,3 R -ACPD but not that by R , S -DHPG. In contrast, the selective group II receptor agonist (1 S ,2 S ,5 R ,6 S )-2-amino-bicyclo-[3.1.0]-hexane-2,6-dicarboxylate (LY 354740) potentiated the response of R , S -DHPG. Finally, 8-(4-chlorophenylthio)-cAMP, a membrane permeant analogue of cAMP, reversed the stimulatory effect of 1 S ,3 R -ACPD and S -4C3HPG on phosphoinositide hydrolysis and [Ca 2+ ] i mobilization, without affecting the response induced by R , S -DHPG. These data suggest that, in neonatal rat cortex, the activation of group II metabotropic glutamate receptors potentiates the phosphoinositide hydrolysis and [Ca 2+ ] i responses mediated by group I metabotropic glutamate receptors.