title: Identification and characterization of a second melanin-concentrating hormone receptor, MCH-2R.
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.
authors.affiliation: Department of Metabolic Disorders, Merck Research Laboratories, P. O. Box 2000, Rahway, NJ 07065, USA. andreas_sailer@merck.com
authors.forename: A W
authors.initials: AW
authors.lastname: Sailer
authors.forename: H
authors.initials: H
authors.lastname: Sano
authors.forename: Z
authors.initials: Z
authors.lastname: Zeng
authors.forename: T P
authors.initials: TP
authors.lastname: McDonald
authors.forename: J
authors.initials: J
authors.lastname: Pan
authors.forename: S S
authors.initials: SS
authors.lastname: Pong
authors.forename: S D
authors.initials: SD
authors.lastname: Feighner
authors.forename: C P
authors.initials: CP
authors.lastname: Tan
authors.forename: T
authors.initials: T
authors.lastname: Fukami
authors.forename: H
authors.initials: H
authors.lastname: Iwaasa
authors.forename: D L
authors.initials: DL
authors.lastname: Hreniuk
authors.forename: N R
authors.initials: NR
authors.lastname: Morin
authors.forename: S J
authors.initials: SJ
authors.lastname: Sadowski
authors.forename: M
authors.initials: M
authors.lastname: Ito
authors.forename: M
authors.initials: M
authors.lastname: Ito
authors.forename: A
authors.initials: A
authors.lastname: Bansal
authors.forename: B
authors.initials: B
authors.lastname: Ky
authors.forename: D J
authors.initials: DJ
authors.lastname: Figueroa
authors.forename: Q
authors.initials: Q
authors.lastname: Jiang
authors.forename: C P
authors.initials: CP
authors.lastname: Austin
authors.forename: D J
authors.initials: DJ
authors.lastname: MacNeil
authors.forename: A
authors.initials: A
authors.lastname: Ishihara
authors.forename: M
authors.initials: M
authors.lastname: Ihara
authors.forename: A
authors.initials: A
authors.lastname: Kanatani
authors.forename: L H
authors.initials: LH
authors.lastname: Van der Ploeg
authors.forename: A D
authors.initials: AD
authors.lastname: Howard
authors.forename: Q
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001921:Brain / Q000378:metabolism*; D016466:CHO Cells; D019556:COS Cells; D002462:Cell Membrane / Q000502:physiology; D002522:Chlorocebus aethiops; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22; D006224:Cricetinae; D005260:Female; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008969:Molecular Sequence Data; D017685:Oncorhynchus keta; D009928:Organ Specificity; D010902:Pituitary Gland / Q000737:chemistry / Q000502:physiology; D011869:Radioligand Assay; D043562:Receptors, G-Protein-Coupled; D011979:Receptors, Pituitary Hormone / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014162:Transfection
chemical_list: C431280:MCHR2 protein, human; D043562:Receptors, G-Protein-Coupled; D011979:Receptors, Pituitary Hormone; D011994:Recombinant Proteins; C092274:melanin-concentrating hormone receptor