Metabotropic glutamate receptor 1-mediated Ca2+ response is potentiated by activation of metabotropic glutamate receptor 3 in the rat hippocampal marginal zone

Metabotropic glutamate receptors (mGluRs) are G-protein coupled receptors (GPCRs) that mediate slow glutamatergic signal transduction and regulate cell excitability in the central nervous system. Group I mGluRs are coupled to G_q/11 proteins and mobilize intracellular Ca²⁺. Group II mGluRs are coupled to G_i/o proteins and inhibit adenylyl cyclase. Hippocampal Cajal-Retzius (CR) cells which regulate neural migration during pre- and post-natal development, express group I and group II mGluRs. Although interactions between GPCRs have been reported, studies on the interactions between GPCRs in native tissues remain insufficient. Previous studies have demonstrated that mGluR1, which belongs to group I mGluRs, mobilizes intracellular Ca²⁺ in CR cells, and this Ca²⁺ response is potentiated by activation of the G_i/o-coupling adenosine A₁ receptor. In this study, the potentiation of intracellular Ca²⁺ mobilization through mGluR1 by the activation of group II mGluRs was demonstrated in hippocampal CR cells. Ca²⁺ imaging in hippocampal slices showed that activation of groupII mGluRs did not induce elevation of intracellular Ca²⁺ concentration, but potentiated mGluR1-induced Ca²⁺ responses. This potentiation was sensitive to a negative allosteric modulator of mGluR3, and several G-protein inhibitors. These results reveal cooperative modulation of intracellular Ca²⁺ mobilization by the two subtypes of mGluRs in hippocampal CR cells.