The receptor for the orexigenic peptide melanin-concentrating hormone is a G-protein-coupled receptor.
Gene-knockout studies of melanin-concentrating hormone (MCH) and its effect on feeding and energy balance have firmly established MCH as an orexigenic (appetite-stimulating) peptide hormone. Here we identify MCH as the ligand for the orphan receptor SLC-1. The rat SLC-1 is activated by nanomolar concentrations of MCH and is coupled to the G protein G alpha i/o. The pattern of SLC-1 messenger RNA expression coincides with the distribution of MCH-containing nerve terminals and is consistent with the known central effects of MCH. Our identification of an MCH receptor could have implications for the development of new anti-obesity therapies.
Lembo
P M
PM
AstraZeneca R&D Montréal, Quebec, Canada.
Grazzini
E
E
Cao
J
J
Hubatsch
D A
DA
Pelletier
M
M
Hoffert
C
C
St-Onge
S
S
Pou
C
C
Labrecque
J
J
Groblewski
T
T
O'Donnell
D
D
Payza
K
K
Ahmad
S
S
Walker
P
P
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000378:metabolism; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D007028:Hypothalamic Hormones / Q000494:pharmacology*; D008164:Luminescent Proteins / Q000032:analysis / Q000235:genetics; D008543:Melanins / Q000494:pharmacology*; D009928:Organ Specificity; D010907:Pituitary Hormones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017481:Receptors, Somatostatin / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D014158:Transcription, Genetic; D014162:Transfection; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D007028:Hypothalamic Hormones; D008164:Luminescent Proteins; C103263:MCHR1 protein, human; C491208:MCHR1 protein, rat; D008543:Melanins; D010907:Pituitary Hormones; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; D011993:Recombinant Fusion Proteins; D010566:Virulence Factors, Bordetella; D049452:Green Fluorescent Proteins; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C019463:melanin-concentrating hormone; D000242:Cyclic AMP; D002118:Calcium