GUANINE-NUCLEOTIDES INHIBIT CAMP ACCUMULATION INDUCED BY METABOTROPICGLUTAMATE-RECEPTOR ACTIVATION

Metabotropic glutamate receptors (mGluRs) have been shown to modulate adenylate cyclase activity via G-proteins. In the present study we rep ort similar results to the previously observed in the literature, show ing that glutamate and the metabotropic agonists, 1S,3R-ACPD or quisqu alate induced cAMP accumulation in hippocampal slices of young rats. M oreover, guanine nucleotides GTP, GDP or GMP, inhibited the glutamate- induced cAMP accumulation. By measuring LDH activity in the buffer sur rounding the slices, we showed that the integrity of the slices was ma intained, indicating that the effect of guanine nucleotides was extrac ellular. GMP, GDP beta-S or Gpp(NH)p abolished quisqualate-induced cAM P accumulation. GDP beta-S or Gpp(NH)p but not GMP inhibited 1S,3R-ACP D-induced cAMP accumulation. The response evoked by glutamate was also abolished by the mGluR antagonists: L-AP3 abolished glutamate-induced cAMP accumulation in a dose-dependent manner and MCPG was effective o nly at the 2 mM dose. DNQX was ineffective. We are reporting here, an inhibition induced by guanine nucleotides, via an extracellular site ( s), similar to the observed with classical glutamate antagonists on a cellular response evoked by mGluR agonists.