G-protein-independent regulation of neuronal metabotropic glutamate signaling by adenosine receptors

Abstract

G-protein-coupled adenosine receptors (ARs) play pivotal roles in synaptic modulation throughout the brain and thereby regulate arousal, cognition, memory, emotion, and neuronal survival. Here we show a novel action of G_i/o-coupled type-1 AR (A1R) on excitatory postsynaptic signaling. In cultured mouse cerebellar Purkinje cells, A1R activation led to acute depression of type-1 metabotropic glutamate receptor (mGluR1)-mediated inward currents and intracellular Ca²⁺ mobilization. By contrast, activation of B-type γ-aminobutyric acid receptor, another G_i/o-coupled receptor, augmented the mGluR1-mediated inward currents. The action of A1R on the inward currents was resistant to a G_i/o-protein inhibitor and was not mimicked by stimulation of the G_s-protein signaling cascade. A1R did not show functional coupling to G_q-protein. These findings demonstrate that A1R reduces postsynaptic mGluR1 signaling independently of the major G-proteins unlike its classical functions. [Jpn J Physiol 54 Suppl:S148 (2004)]