Identification of melanin concentrating hormone (MCH) as the natural ligand for the orphan somatostatin-like receptor 1 (SLC-1)

FEBS Lett. 1999 Sep 3;457(3):522-4. doi: 10.1016/s0014-5793(99)01092-3.


To identify possible ligands of the orphan somatostatin-like receptor 1 (SLC-1), rat brain extracts were analyzed by using the functional expression system of Xenopus oocytes injected with cRNAs encoding SLC-1 and G protein-gated inwardly rectifying potassium channels (GIRK). A strong inward current was observed with crude rat brain extracts which upon further purification by cation exchange chromatography and high performance liquid chromatography (HPLC) yielded two peptides with a high agonist activity. Mass spectrometry and partial peptide sequencing revealed that one peptide is identical with the neuropeptide melanin concentrating hormone (MCH), the other represents a truncated version of MCH lacking the three N-terminal amino acid residues. Xenopus oocytes expressing the MCH receptor responded to nM concentrations of synthetic MCH not only by the activation of GIRK-mediated currents but also by the induction of Ca(2+) dependent chloride currents mediated by phospholipase C. This indicates that the MCH receptor can couple either to the G(i)- or G(q)-mediated signal transduction pathway, suggesting that MCH may serve for a number of distinct brain functions including food uptake behavior.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Brain Chemistry*
  • Chromatography, High Pressure Liquid
  • Electrophysiology
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • Hypothalamic Hormones / isolation & purification
  • Hypothalamic Hormones / metabolism*
  • Hypothalamic Hormones / pharmacology
  • Ligands
  • Mass Spectrometry
  • Melanins / isolation & purification
  • Melanins / metabolism*
  • Melanins / pharmacology
  • Molecular Sequence Data
  • Oocytes / physiology
  • Pituitary Hormones / isolation & purification
  • Pituitary Hormones / metabolism*
  • Pituitary Hormones / pharmacology
  • Potassium Channels / genetics
  • Potassium Channels / metabolism
  • Potassium Channels, Inwardly Rectifying*
  • Rats
  • Receptors, Somatostatin / genetics
  • Receptors, Somatostatin / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Signal Transduction
  • Tissue Extracts / metabolism
  • Xenopus


  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • Hypothalamic Hormones
  • Ligands
  • MCHR1 protein, rat
  • Melanins
  • Pituitary Hormones
  • Potassium Channels
  • Potassium Channels, Inwardly Rectifying
  • Receptors, Somatostatin
  • Recombinant Proteins
  • Tissue Extracts
  • melanin-concentrating hormone
  • GTP-Binding Proteins