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Molecular characterization of the melanin-concentrating-hormone receptor
Author(s): Saito Y, Nothacker HP, Wang ZW, Lin SHS, Leslie F, Civelli O
Source: NATURE    Volume: 400    Issue: 6741    Pages: 265-269    Published: JUL 15 1999  
Times Cited: 294     References: 30     
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 molecules(1). 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 receptors(2,3). 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 behaviour(5,6). We demonstrate that nanomolar concentrations of MCH strongly activate SLC-1-related pathways through G alpha(i) and/or G alpha(q) 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.
Document Type: Article
Language: English
Reprint Address: Civelli, O (reprint author), Univ Calif Irvine, Dept Pharmacol, Irvine, CA 92697 USA
Addresses:
1. Univ Calif Irvine, Dept Pharmacol, Irvine, CA 92697 USA
2. Univ Calif Irvine, Dept Anat & Neurobiol, Irvine, CA 92697 USA
3. Univ Calif Irvine, Dept Dev & Cell Biol, Irvine, CA 92697 USA
Publisher: MACMILLAN MAGAZINES LTD, PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
Subject Category: Multidisciplinary Sciences
IDS Number: 217MP
ISSN: 0028-0836
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