The enhancement and the inhibition of noradrenaline-induced cyclic AMP accumulation in rat brain by stimulation of metabotropic glutamate receptors.

The actions of several metabotropic glutamate receptor agonists and antagonists on noradrenaline (NA)-stimulated [3H]-cyclic AMP accumulation were investigated in rat cerebral cortical slices. Quisqualate (QUIS), L-2-amino-3-phosphonopropionic acid (L-AP3) and glutamate (GLU) elicited concentration-dependent inhibition of (NA)-stimulated [3H]-cyclic AMP accumulation. In contrast (2S,3S,4S)-alpha-(Carboxy-cyclopropyl)glycine (L-CCGI), 1-Aminocyclo-pentane-1S,3R-dicarboxylate (1S,3R-ACPD), ibotenate (IBO) and (RS)-4-carboxy-3-hydroxy-phenylglycine (CHPG) elicited a concentration-dependent enhancement of NA-stimulated [3H]-cyclic AMP accumulation. A putative mGluR antagonist-L-AP3, inhibited the 1S,3R-ACPD-induced enhancement of the action of NA on [3H]-cyclic AMP accumulation in a biphasic manner with an IC50 of 4.5 microM for the high affinity site, which represented 65% of the total and an IC50 of 283 microM for the low affinity site.