Neuromedin U (NMU) is a neuropeptide with potent activity on smooth muscle which 
was isolated first from porcine spinal cord and later from other species. It is 
widely distributed in the gut and central nervous system. Peripheral activities 
of NMU include stimulation of smooth muscle, increase of blood pressure, 
alteration of ion transport in the gut, control of local blood flow and 
regulation of adrenocortical function. An NMU receptor has not been molecularly 
identified. Here we show that the previously described orphan G-protein-coupled 
receptor FM-3 (ref. 15) and a newly discovered one (FM-4) are cognate receptors 
for NMU. FM-3, designated NMU1R, is abundantly expressed in peripheral tissues 
whereas FM-4, designated NMU2R, is expressed in specific regions of the brain. 
NMU is expressed in the ventromedial hypothalamus in the rat brain, and its 
level is significantly reduced following fasting. Intracerebroventricular 
administration of NMU markedly suppresses food intake in rats. These findings 
provide a molecular basis for the biochemical activities of NMU and may indicate 
that NMU is involved in the central control of feeding.