PMID- 10421368
OWN - NLM
STAT- MEDLINE
DCOM- 19990805
LR  - 20200311
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 400
IP  - 6741
DP  - 1999 Jul 15
TI  - Molecular characterization of the melanin-concentrating-hormone receptor.
PG  - 265-9
AB  - 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. 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. We show that the natural ligand of this
      receptor is the neuropeptide melanin-concentrating hormone (MCH). MCH is a cyclic
      peptide that regulates a variety of functions in the mammalian brain, in
      particular feeding behaviour. 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.
FAU - Saito, Y
AU  - Saito Y
AD  - Department of Pharmacology, University of California, Irvine 92697-4625, USA.
FAU - Nothacker, H P
AU  - Nothacker HP
FAU - Wang, Z
AU  - Wang Z
FAU - Lin, S H
AU  - Lin SH
FAU - Leslie, F
AU  - Leslie F
FAU - Civelli, O
AU  - Civelli O
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Hypothalamic Hormones)
RN  - 0 (Ligands)
RN  - 0 (MCHR1 protein, human)
RN  - 0 (MCHR1 protein, rat)
RN  - 0 (Melanins)
RN  - 0 (Pituitary Hormones)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Somatostatin)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 67382-96-1 (melanin-concentrating hormone)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Brain/metabolism
MH  - CHO Cells
MH  - Cell Line
MH  - Chromatography, High Pressure Liquid
MH  - Cricetinae
MH  - Feeding Behavior/physiology
MH  - GTP-Binding Proteins/genetics/*metabolism/physiology
MH  - Humans
MH  - Hypothalamic Hormones/*metabolism/physiology
MH  - Ligands
MH  - Melanins/*metabolism/physiology
MH  - Molecular Sequence Data
MH  - Pituitary Hormones/*metabolism/physiology
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Receptors, Somatostatin/genetics/*metabolism/physiology
MH  - Recombinant Fusion Proteins/metabolism
MH  - Salmon
MH  - Sequence Homology, Amino Acid
MH  - Signal Transduction
MH  - Tissue Distribution
MH  - Transfection
EDAT- 1999/07/27 10:00
MHDA- 2001/03/23 10:01
CRDT- 1999/07/27 10:00
PHST- 1999/07/27 10:00 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/07/27 10:00 [entrez]
AID - 10.1038/22321 [doi]
PST - ppublish
SO  - Nature. 1999 Jul 15;400(6741):265-9. doi: 10.1038/22321.