Melanin-concentrating hormone (MCH), a cyclic nonadecapeptide, is predominantly expressed in mammalian neurons located in the zona incerta and lateral hypothalamus. Current interest in MCH relates to its role in the control of feeding behaviour. Two receptors for MCH were recently found: MCH-R-1 and MCH-R-2. We show here by RT-PCR analysis and immunofluorescence studies that the human neuroblastoma cell line Kelly expresses MCH and MCH-R-1 but not MCH-R-2. In competition assays using I-125-labelled MCH an inhibitory concentration 50% (IC50) of 76 nM was determined for MCH, indicating a high affinity of Kelly cells for MCH. MCH induces mitogen-activated protein kinase (MAPK) phosphorylation in Kelly cells but no increase in the intracellular free Ca2+ concentration. This suggests that MCH signals via Galpha(1)/Galpha(0) in these cells. The presence and functionality of MCH-R-1 renders this neuronal cell a very useful model for future structure-activity studies in a physiological environment mimicking the human brain for the evaluation of potential appetite-regulating drugs. (C) 2002 Elsevier Science (USA). All rights reserved.