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The receptor for the orexigenic peptide melanin-concentrating hormone is a G-protein-coupled receptor

Nature Cell Biology volume 1, pages 267–271 (1999)Cite this article

Abstract

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 Gαi/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.

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Figure 1: Intracellular Ca2+ mobilization induced by MCH in cells expressing SLC-1 is PTX-sensitive.
Figure 2: MCH induces internalization of the GFP-tagged SLC-1.
Figure 3: In situ hybridization autoradiographs showing localization of SLC-1 mRNA in adult rat CNS.

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Acknowledgements

We thank G. Milligan for providing HEK 293 cells stably transfected with GFP-tagged TRH receptor-1; A. Beaudet for advice on receptor-internalization studies; and G. Keil for critical analysis of the manuscript.

Correspondence and requests for materials should be addressed to S.A.

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  1. AstraZeneca R&D Montréal, 7171 Frederick-Banting, Ville St Laurent, H4S 1Z9, Quebec, Canada

    Paola M.C. Lembo, Eric Grazzini, Jack Cao, Douglas A. Hubatsch, Manon Pelletier, Cyrla Hoffert, Stephane St-Onge, Chantevy Pou, Jean Labrecque, Thierry Groblewski, Dajan O’Donnell, Kemal Payza, Sultan Ahmad & Philippe Walker

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Correspondence to Sultan Ahmad.

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Lembo, P., Grazzini, E., Cao, J. et al. The receptor for the orexigenic peptide melanin-concentrating hormone is a G-protein-coupled receptor. Nat Cell Biol 1, 267–271 (1999). https://doi.org/10.1038/12978

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