Melanin-concentrating hormone is the cognate ligand for the orphan G-protein-coupled receptor SLC-1

Jon Chambers (), Robert S. Ames, Derk Bergsma, Alison Muir, Laura R. Fitzgerald, Guillaume Hervieu, George M. Dytko, James J. Foley, John Martin, Wu-Schyong Liu, Janet Park, Catherine Ellis, Subinay Ganguly, Susan Konchar, Jane Cluderay, Ron Leslie, Shelagh Wilson and Henry M. Sarau
Additional contact information
Jon Chambers: Departments of Molecular Screening Technologies
Robert S. Ames: Departments of Molecular Biology
Derk Bergsma: Departments of Molecular Biology
Alison Muir: Departments of Molecular Screening Technologies
Laura R. Fitzgerald: Renal Pharmacology,
Guillaume Hervieu: Neuroscience, New Frontiers Science Park
George M. Dytko: Renal Pharmacology,
James J. Foley: Pulmonary Pharmacology
John Martin: Protein Biochemistry
Wu-Schyong Liu: Protein Biochemistry
Janet Park: Departments of Molecular Screening Technologies
Catherine Ellis: Departments of Molecular Biology
Subinay Ganguly: Gene Expression Sciences SmithKline Beecham Pharmaceuticals
Susan Konchar: Gene Expression Sciences SmithKline Beecham Pharmaceuticals
Jane Cluderay: Neuroscience, New Frontiers Science Park
Ron Leslie: Neuroscience, New Frontiers Science Park
Shelagh Wilson: Departments of Molecular Screening Technologies
Henry M. Sarau: Pulmonary Pharmacology

Nature, 1999, vol. 400, issue 6741, 261-265

Abstract: Abstract The underlying causes of obesity are poorly understood but probably involve complex interactions between many neurotransmitter and neuropeptide systems involved in the regulation of food intake and energy balance. Three pieces of evidence indicate that the neuropeptide melanin-concentrating hormone (MCH) is an important component of this system. First, MCH stimulates feeding when injected directly into rat brains1,2; second, the messenger RNA for the MCH precursor is upregulated in the hypothalamus of genetically obese mice and in fasted animals1; and third, mice lacking MCH eat less and are lean3. MCH antagonists might, therefore, provide a treatment for obesity. However, the development of such molecules has been hampered because the identity of the MCH receptor has been unknown until now. Here we show that the 353-amino-acid human orphan G-protein-coupled receptor SLC-1 (ref. 4) expressed in HEK293 cells binds MCH with sub-nanomolar affinity, and is stimulated by MCH to mobilize intracellular Ca2+ and reduce forskolin-elevated cyclic AMP levels. We also show that SLC-1 messenger RNA and protein is expressed in the ventromedial and dorsomedial nuclei of the hypothalamus, consistent with a role for SLC-1 in mediating the effects of MCH on feeding.

Date: 1999
References: Add references at CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/22313 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:400:y:1999:i:6741:d:10.1038_22313

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/22313

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().