Identification and characterization of a melanin-concentrating hormone receptor

Melanin-concentrating hormone (MCH), a neuropeptide expressed in central an d peripheral nervous systems, plays an important role in the control of fee ding behaviors and energy metabolism. An orphan G protein-coupled receptor (SLC-1/GPR24) has recently been identified as a receptor for MCH (MCHR1). W e report here the identification and characterization of a G protein-couple d receptor as the MCH receptor subtype 2 (MCHR2). MCHR2 has higher protein sequence homology to MCHR1 than any other G protein-coupled receptor. The e xpression of MCHR2 has been detected in many regions of the brain. In contr ast to MCHR1. which is intronless in the coding region and is located at th e chromosomal locus 22q13.3, the MCHR2 gene has multiple exons and is mappe d to locus 6q21. MCHR2 is specifically activated by nanomolar concentration s of MCH, binds to MCH with high affinity, and signals through Gq protein. This discovery is important for a full understanding of MCH biology and the development of potential therapeutics for diseases involving MCH. includin g obesity.