PMID- 10421367
OWN - NLM
STAT- MEDLINE
DCOM- 19990805
LR  - 20131121
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 400
IP  - 6741
DP  - 1999 Jul 15
TI  - Melanin-concentrating hormone is the cognate ligand for the orphan
      G-protein-coupled receptor SLC-1.
PG  - 261-5
AB  - The underlying causes of obesity are poorly understood but probably involve
      complex interactions between many neurotransmitter and neuropeptide systems
      involved in the regulation of food intake and energy balance. Three pieces of
      evidence indicate that the neuropeptide melanin-concentrating hormone (MCH) is an
      important component of this system. First, MCH stimulates feeding when injected
      directly into rat brains; second, the messenger RNA for the MCH precursor is
      upregulated in the hypothalamus of genetically obese mice and in fasted animals; 
      and third, mice lacking MCH eat less and are lean. MCH antagonists might,
      therefore, provide a treatment for obesity. However, the development of such
      molecules has been hampered because the identity of the MCH receptor has been
      unknown until now. Here we show that the 353-amino-acid human orphan
      G-protein-coupled receptor SLC-1 expressed in HEK293 cells binds MCH with
      sub-nanomolar affinity, and is stimulated by MCH to mobilize intracellular Ca2+
      and reduce forskolin-elevated cyclic AMP levels. We also show that SLC-1
      messenger RNA and protein is expressed in the ventromedial and dorsomedial nuclei
      of the hypothalamus, consistent with a role for SLC-1 in mediating the effects of
      MCH on feeding.
FAU - Chambers, J
AU  - Chambers J
AD  - Department of Molecular Screening Technologies, New Frontiers Science Park,
      SmithKline Beecham Pharmaceuticals, Harlow, Essex, UK. Jon_Chambers-1@sbphrd.com
FAU - Ames, R S
AU  - Ames RS
FAU - Bergsma, D
AU  - Bergsma D
FAU - Muir, A
AU  - Muir A
FAU - Fitzgerald, L R
AU  - Fitzgerald LR
FAU - Hervieu, G
AU  - Hervieu G
FAU - Dytko, G M
AU  - Dytko GM
FAU - Foley, J J
AU  - Foley JJ
FAU - Martin, J
AU  - Martin J
FAU - Liu, W S
AU  - Liu WS
FAU - Park, J
AU  - Park J
FAU - Ellis, C
AU  - Ellis C
FAU - Ganguly, S
AU  - Ganguly S
FAU - Konchar, S
AU  - Konchar S
FAU - Cluderay, J
AU  - Cluderay J
FAU - Leslie, R
AU  - Leslie R
FAU - Wilson, S
AU  - Wilson S
FAU - Sarau, H M
AU  - Sarau HM
LA  - eng
PT  - Journal Article
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Hypothalamic Hormones)
RN  - 0 (Ligands)
RN  - 0 (MCHR1 protein, human)
RN  - 0 (Mch1r protein, mouse)
RN  - 0 (Mch1r protein, rat)
RN  - 0 (Melanins)
RN  - 0 (Pituitary Hormones)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Somatostatin)
RN  - 0 (Recombinant Proteins)
RN  - 67382-96-1 (melanin-concentrating hormone)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Alternative Splicing
MH  - Amino Acid Sequence
MH  - Animals
MH  - Calcium/metabolism
MH  - Cell Line
MH  - Cloning, Molecular
MH  - Cyclic AMP/metabolism
MH  - Feeding Behavior
MH  - GTP-Binding Proteins/genetics/*metabolism
MH  - Humans
MH  - Hypothalamic Hormones/*metabolism
MH  - Hypothalamus/metabolism
MH  - In Situ Hybridization
MH  - Ligands
MH  - Melanins/*metabolism
MH  - Mice
MH  - Molecular Sequence Data
MH  - Pituitary Hormones/*metabolism
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Receptors, Somatostatin/genetics/*metabolism
MH  - Recombinant Proteins/metabolism
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 - 10.1038/22313 [doi]
PST - ppublish
SO  - Nature. 1999 Jul 15;400(6741):261-5. doi: 10.1038/22313.