Endogenous melanin-concentrating hormone receptor SLC-1 in human melanoma SK-MEL-37 cells.

Abstract

Melanin-concentrating hormone (MCH) is a hypothalamic neuropeptide that regulates several physiological functions. The orphan G protein-coupled receptors SLC-1 and MCHR2 were recently found to bind MCH with high affinity. We show here that the human melanoma cell line SK-MEL-37 expresses SLC-1 mRNA but not MCHR2 by RT-PCR analysis and immunofluorescence studies. Using Chinese hamster ovary cells and 293 cells overexpressing SLC-1 by cDNA transfection, it was shown that SLC-1 coupled to both G alpha(i)/G alpha(o) and G alpha(q) proteins. In SK-MEL-37 cells, MCH inhibited forskolin-stimulated cyclic AMP accumulation and induced mitogen-activated protein kinase (MAPK) in a pertussis toxin-(PTX)-sensitive manner. The MAPK activity leads to the production of phosphorylated forms of p42/p44 MAPK. However, an increase in the intracellular free Ca(2+) concentration was not elicited by MCH in SK-MEL-37 cells. These results show that SLC-1 is coupled only to PTX-sensitive G alpha(i)/G alpha(o) in SK-MEL-37 cells. This study provides for the first time a skin-derived cellular model to analyze the molecular mechanism of the MCH signaling pathway.

• Authors: Y Saito, Z Wang, K Hagino-Yamagishi, O Civelli, S Kawashima, K Maruyama
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 289 Issue 1 Pg. 44-50 (Nov 23 2001) ISSN: 0006-291X [Print] United States
• PMID: 11708774 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2001 Academic Press.

Chemical References

• Hypothalamic Hormones
• Melanins
• Pituitary Hormones
• RNA, Messenger
• RNA, Neoplasm
• Receptors, Pituitary Hormone
• Virulence Factors, Bordetella
• melanin-concentrating hormone receptor
• Colforsin
• melanin-concentrating hormone
• Cyclic AMP
• Pertussis Toxin
• Mitogen-Activated Protein Kinases
• Heterotrimeric GTP-Binding Proteins

Topics

• Animals
• CHO Cells
• Colforsin (pharmacology)
• Cricetinae
• Cyclic AMP (metabolism)
• Enzyme Induction (drug effects)
• Heterotrimeric GTP-Binding Proteins (metabolism)
• Humans
• Hypothalamic Hormones (metabolism, pharmacology)
• Melanins (metabolism, pharmacology)
• Melanoma (genetics, metabolism)
• Mitogen-Activated Protein Kinases (biosynthesis)
• Models, Biological
• Pertussis Toxin
• Phosphorylation
• Pituitary Hormones (metabolism, pharmacology)
• RNA, Messenger (genetics, metabolism)
• RNA, Neoplasm (genetics, metabolism)
• Receptors, Pituitary Hormone (genetics, metabolism)
• Signal Transduction
• Tumor Cells, Cultured
• Virulence Factors, Bordetella (pharmacology)