Identification and pharmacological characterization of a novel human melanin-concentrating hormone receptor, MCH-R2

Melanin-concentrating hormone (MCH) is a neuropeptide highly expressed in t he brain that regulates several physiological functions mediated by recepto rs in the G protein-coupled receptor family. Recently an orphan receptor, S LC-1, has been identified as an MCH receptor (MCH-RI). Herein we identify a nd characterize a novel receptor for human MCH (MCH-R2). The receptor is co mposed of 340 amino acids encoded by a 1023-base pair cDNA and is 35% homol ogous to SLC-1. I-125-MCH specifically bound to Chinese hamster ovary cells stably expressing MCH-R2. MCH stimulated dose-dependent increases in intra cellular free Ca2+ and inositol phosphate production in these cells but did not affect cAMP production. The pharmacological profile for mammalian MCH, [Phe(13),Tyr(19)]MCH, and salmon MCH at MCH-R2 differed compared with MCH- R1 as assessed by intracellular signaling and radioligand binding assays. T he EC50 in signaling assays and the IC50 in radioligand binding assays of s almon MCH was an order of magnitude higher than mammalian MCH at MCH-R2. By comparison, the EC50 and IC50 values of salmon MCH and mammalian MCH at MC H-R1 were relatively similar. Blot hybridization revealed exclusive express ion of MCH-R2 m-RNA in several distinct brain regions, particularly in the cortical area, suggesting the involvement of MCH-R2 in the central regulati on of MCH-mediated functions.