Endogenous receptor for melanin-concentrating hormone in human neuroblastoma Kelly cells.
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 125I-labelled MCH an inhibitory concentration 50% (IC(50)) of 76nM 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 Ca(2+) concentration. This suggests that MCH signals via Galpha(i)/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.
Schlumberger
Sophie E
SE
Laboratory of Endocrinology, Department of Research (ZLF), University Hospital and University Children's Hospital, Hebelstrasse 20, CH-4031, Basel, Switzerland. Sophie.Schlumberger@free.fr
Jäggin
Verena
V
Tanner
Heidi
H
Eberle
Alex N
AN
D020013:Calcium Signaling; D002460:Cell Line; D005455:Fluorescent Antibody Technique; D006367:HeLa Cells; D006801:Humans; D020935:MAP Kinase Signaling System; D009447:Neuroblastoma; D009474:Neurons / Q000737:chemistry*; D012333:RNA, Messenger / Q000096:biosynthesis; D011979:Receptors, Pituitary Hormone / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D011979:Receptors, Pituitary Hormone; C092274:melanin-concentrating hormone receptor