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Molecular characterization of the melanin-concentrating-hormone receptor

Author

Listed:
  • Yumiko Saito

    (Department of Pharmacology)

  • Hans-Peter Nothacker

    (Department of Pharmacology)

  • Zhiwei Wang

    (Department of Pharmacology)

  • Steven H. S. Lin

    (Department of Pharmacology)

  • Frances Leslie

    (Department of Pharmacology
    Department of Anatomy and Neurobiology)

  • Olivier Civelli

    (Department of Pharmacology
    University of California, Irvine)

Abstract

Orphan G-protein-coupled receptors (GPCRs) are cloned proteins with structural characteristics common to the GPCRs but that bind unidentified ligands. Orphan GPCRs have been used as targets to identify novel transmitter molecules1. Here we describe the isolation from brain extracts and the characterization of the natural ligand of a particular orphan GPCR (SLC-1) that is sequentially homologous to the somatostatin receptors2,3. We show that the natural ligand of this receptor is the neuropeptide melanin-concentrating hormone (MCH)4. MCH is a cyclic peptide that regulates a variety of functions in the mammalian brain, in particular feeding behaviour5,6. We demonstrate that nanomolar concentrations of MCH strongly activate SLC-1-related pathways through Gαi and/or Gαq proteins. We have analysed the tissue localization of the MCH receptor and find that it is expressed in several brain regions, in particular those involved in olfactory learning and reinforcement mechanisms, indicating that therapies targeting the MCH receptor should act on the neuronal regulation of food consumption.

Suggested Citation

  • Yumiko Saito & Hans-Peter Nothacker & Zhiwei Wang & Steven H. S. Lin & Frances Leslie & Olivier Civelli, 1999. "Molecular characterization of the melanin-concentrating-hormone receptor," Nature, Nature, vol. 400(6741), pages 265-269, July.
    • Handle: RePEc:nat:nature:v:400:y:1999:i:6741:d:10.1038_22321
    DOI: 10.1038/22321
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    Cited by:

    1. Joram D Mul & Susanne E la Fleur & Pim W Toonen & Anthonieke Afrasiab-Middelman & Rob Binnekade & Dustin Schetters & Michel M M Verheij & Robert M Sears & Judith R Homberg & Anton N M Schoffelmeer & R, 2011. "Chronic Loss of Melanin-Concentrating Hormone Affects Motivational Aspects of Feeding in the Rat," PLOS ONE, Public Library of Science, vol. 6(5), pages 1-13, May.
    2. Kenkichi Takase & Kenichi Kikuchi & Yousuke Tsuneoka & Satoko Oda & Masaru Kuroda & Hiromasa Funato, 2014. "Meta-Analysis of Melanin-Concentrating Hormone Signaling-Deficient Mice on Behavioral and Metabolic Phenotypes," PLOS ONE, Public Library of Science, vol. 9(6), pages 1-15, June.

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