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. Epub 2001 Jun 12.

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.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Brain / metabolism*
  • CHO Cells
  • COS Cells
  • Cell Membrane / physiology
  • Chlorocebus aethiops
  • Chromosome Mapping
  • Chromosomes, Human, Pair 22*
  • Cricetinae
  • Female
  • Humans
  • In Situ Hybridization
  • Male
  • Molecular Sequence Data
  • Oncorhynchus keta
  • Organ Specificity
  • Pituitary Gland / chemistry
  • Pituitary Gland / physiology
  • Radioligand Assay
  • Receptors, G-Protein-Coupled
  • Receptors, Pituitary Hormone / chemistry
  • Receptors, Pituitary Hormone / genetics*
  • Receptors, Pituitary Hormone / metabolism*
  • Receptors, Pituitary Hormone / physiology*
  • Recombinant Proteins / metabolism
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Transfection

Substances

  • MCHR2 protein, human
  • Receptors, G-Protein-Coupled
  • Receptors, Pituitary Hormone
  • Recombinant Proteins
  • melanin-concentrating hormone receptor

Associated data

  • GENBANK/AQ747249
  • GENBANK/AY029596