Identification and characterization of a second melanin-concentrating hormone receptor, MCH-2R.
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.
Sailer
A W
AW
Department of Metabolic Disorders, Merck Research Laboratories, P. O. Box 2000, Rahway, NJ 07065, USA. andreas_sailer@merck.com
Sano
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Zeng
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McDonald
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Pan
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Pong
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Feighner
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Tan
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Fukami
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Iwaasa
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Hreniuk
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Morin
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Sadowski
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Ito
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Ito
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Bansal
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Figueroa
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Jiang
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Austin
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MacNeil
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Ishihara
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Ihara
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Kanatani
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Van der Ploeg
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Howard
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Liu
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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
C431280:MCHR2 protein, human; D043562:Receptors, G-Protein-Coupled; D011979:Receptors, Pituitary Hormone; D011994:Recombinant Proteins; C092274:melanin-concentrating hormone receptor