In 1998, we purified a novel neuropeptide orexin and showed that this peptide plays pivotal roles in the regulation of appetite and sleep. In this ERATO project, we showed that the administration of orexin could actually rescue the narcoleptic symptoms in orexin knockout mice.
We also vigorously performed the “deorphanization” of orphan GPCRs during the project, and identified novel ligands for GPR103 and GPR7/8. We showed that the ligand of GPR103 has an essential function in regulating appetite and blood pressure. Through the analysis of knockout mice, we have clarified that the ligands for GPR7/8 (= NPB and NPW) have important roles in the homeostasis of the body, such as energy metabolism and stress responses.