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  2. Identification and characterization of a second melanin-concentrating hormone receptor, MCH-2R

Identification and characterization of a second melanin-concentrating hormone receptor, MCH-2R

  • Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7564-9. doi: 10.1073/pnas.121170598.
A W Sailer 1 H Sano Z Zeng T P McDonald J Pan S S Pong S D Feighner C P Tan T Fukami H Iwaasa D L Hreniuk N R Morin S J Sadowski M Ito M Ito A Bansal B Ky D J Figueroa Q Jiang C P Austin D J MacNeil A Ishihara M Ihara A Kanatani L H Van der Ploeg A D Howard Q Liu
Affiliations

Affiliation

  • 1 Department of Metabolic Disorders, Merck Research Laboratories, P. O. Box 2000, Rahway, NJ 07065, USA. andreas_sailer@merck.com
Abstract

Melanin-concentrating hormone (MCH) is a 19-aa cyclic neuropeptide originally isolated from chum salmon pituitaries. Besides its effects on the aggregation of melanophores in fish several lines of evidence suggest that in mammals MCH functions as a regulator of energy homeostasis. Recently, several groups reported the identification of an orphan G protein-coupled receptor as a receptor for MCH (MCH-1R). We hereby report the identification of a second human MCH receptor termed MCH-2R, which shares about 38% amino acid identity with MCH-1R. MCH-2R displayed high-affinity MCH binding, resulting in inositol phosphate turnover and release of intracellular calcium in mammalian cells. In contrast to MCH-1R, MCH-2R signaling is not sensitive to pertussis toxin and MCH-2R cannot reduce forskolin-stimulated cAMP production, suggesting an exclusive G(alpha)q coupling of the MCH-2R in cell-based systems. Northern blot and in situ hybridization analysis of human and monkey tissue shows that expression of MCH-2R mRNA is restricted to several regions of the brain, including the arcuate nucleus and the ventral medial hypothalamus, areas implicated in regulation of body weight. In addition, the human MCH-2R gene was mapped to the long arm of chromosome 6 at band 6q16.2-16.3, a region reported to be associated with cytogenetic abnormalities of obese patients. The characterization of a second mammalian G protein-coupled receptor for MCH potentially indicates that the control of energy homeostasis in mammals by the MCH neuropeptide system may be more complex than initially anticipated.

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