The receptor for the orexigenic peptide melanin-concentrating hormone is aG-protein-coupled receptor

Gene-knockout studies of melanin-concentrating hormone (MCH) and its effect on feeding and energy balance have firmly established MCH as an orexigenic (appetite-stimulating) peptide hormone. Here we identify MCH as the ligand for the orphan receptor SLC-1. The rat SLC-1 is activated by nanomolar con centrations of MCH and is coupled to the G protein G alpha(i/o). The patter n of SLC-1 messenger RNA expression coincides with the distribution of MCH- containing nerve terminals and is consistent with the known central effects of MCH, Our identification of an MCH receptor could have implications for the development of new anti-obesity therapies.