Identification and characterization of two neuromedin U receptors differentially expressed in peripheral tissues and the central nervous system

Two structurally related, G-protein-coupled receptors were identified as re ceptors for the neuropeptide, neuromedin U, This peptide is found in highes t levels in the gut and genitourinary system where it potently contracts sm ooth muscle but is also expressed in the spinal cord and discrete regions o f the brain. Binding sites for neuromedin U have been characterized in rat uterus, however, little is known about the activity of this peptide in the regions of the central nervous system where it is expressed. The receptors characterized in this report are activated by neuromedin U at nanomolar pot ency in heterologous expression systems and bind radiolabeled neuromedin U with high affinity. Localization of the receptor RNA by quantitative revers e transcription-polymerase chain reaction in a variety of human tissues sho ws distinct expression patterns for the two receptors, NMU1 is expressed pr edominantly in peripheral tissues, whereas NMU2 is more highly expressed in the central nervous system. Identification of neuromedin U receptor subtyp es will greatly aid in the determination of the physiological roles of this peptide.