Glutamate and gamma-aminobutyric acid (GABA) are both major neurotransmitters in the mammalian central nervous system. Type 1 metabotropic glutamate receptor (mGluR1) and GABA_B receptor (GBR) are G protein-coupled receptors (GPCRs) which are excited by glutamate and GABA, respectively. mGluR1 is mainly expressed at the post-synaptic membrane of cerebellar Purkinje cells and plays a crucial role in cerebellar motor learning via G_q protein. GBR is expressed at pre- and post-synaptic membranes of various types of neurons including cerebellar Purkinje cells and exerts inhibitory action via G_i protein. Previous studies have suggested that GBR is co-expressed with mGluR1 at the post-synaptic membrane of cerebellar Purkinje cells, and interaction between GBR and mGluR1 promotes the neuronal function of mGluR1. In this report, to clarify the details of the interaction between mGluR1 and GBR, we evaluated their complex formation and signal transduction using cell lines. We revealed that GBR form complexes with mGluR1 and that mGluR1 and GBR mutually modulate their signal transductions. Furthermore, we demonstrated the possibility of that these signal modulations are independent of G proteins. These findings provide new insights into the mechanism of the regulatory actions of the two important GPCRs for synaptic transmission and neuronal function.