Activation of adenosine A 1 receptor potentiates metabotropic glutamate receptor 1-mediated Ca 2+ mobilization in the rat hippocampal marginal zone.

Two subtypes of group I metabotropic glutamate receptors (mGluRs), mGluR1 and mGluR5, participate in the regulation of cell excitability and synaptic plasticity in the central nervous system. They couple to the Gq/11 protein and release Ca2+ from the intracellular stores. In the marginal zone of the neonatal hippocampus, Cajal-Retzius (CR) cells, which control radial migration of neurons, express the subtype mGluR1. The adenosine A1 receptor (A1 R) is also G-protein coupled and is extensively expressed in the central nervous system. The interactions among G-protein-coupled receptors have been predicted previously, however, there is insufficient evidence of functional interactions between naturally occurring receptors. In this study, potentiation of the mGluR1-mediated response by A1 R activation was demonstrated in hippocampal CR cells. Fluorescence imaging revealed that the application of A1 R agonists intensified mGluR1-induced elevation of intracellular Ca2+ concentration ([Ca2+ ]i ). Activation of A1 R did not change [Ca2+ ]i . The potentiated responses were independent of extracellular Ca2+ and prevented by the Gi inhibitor. The potentiation of mGluR1-induced [Ca2+ ]i . elevation was also enhanced by mGluR2/3 activation. These results suggest that mGluR1 and A1 R cooperatively influence postnatal hippocampal development by facilitating Ca2+ mobilization in CR cells.