Levodopa (L-DOPA) therapy is the gold standard for the treatment with Parkinson's disease. The pharmacological actions of L-DOPA have been believed to be mediated through its conversion to dopamine. On the contrary, we propose that L-DOPA is a neurotransmitter. We recently identified G-protein coupled receptor (GPCR) GPR143, a gene product of ocular albinism-1, as a receptor for L-DOPA. In the course of our pharmacological analysis of Gpr143 gene-deficient (GPR143-KO) mice, we found that the pressor response to intravenous injection of an adrenaline alpha1 receptor (ADRA1) agonist phenylephrine was attenuated in GPR143-KO mice when compared to wild type (WT) mice. The contractile response to phenylephrine in blood vessels from GPR143-KO mice was also attenuated when compared to WT mice. FRET analysis and in situ proximity ligation assay revealed that GPR143 formed heteromeric complexes with ADRA1 in vitro and vivo. Furthermore, GPR143 interacted a specific subset of GPCRs and modified their signal transductions. These results suggest that GPR143 fine-tunes the GPCR signaling through heteromeric complexes.