Purification and identification of neuromedin U as an endogenous ligand for an orphan receptor GPR66 (FM3)

Biochem Biophys Res Commun. 2000 Sep 24;276(2):435-8. doi: 10.1006/bbrc.2000.3502.


GPR66 is an orphan G-protein-coupled receptor (GPCR) whose structure is similar to the ghrelin and motilin receptors. We have tried to purify a natural ligand for GPR66 in rat tissues and identified a 23-amino-acid peptide as the endogenous ligand. Sequence analysis revealed the peptide as neuromedin U (NMU), a smooth-muscle-contracting peptide that was first purified from porcine spinal cord by our group. NMU binds to GPR66-expressing cells with high specificity to induce intracellular calcium mobilization. When NMU was injected intracerebroventricularly (ICV) into rats, it potently suppressed food intake. In contrast, ICV injection of NMU-antibody increased food intake. These results suggest that NMU is a potent endogenous anorexic peptide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CHO Cells
  • Cricetinae
  • Ligands
  • Membrane Proteins*
  • Molecular Sequence Data
  • Neuropeptides / chemistry
  • Neuropeptides / isolation & purification*
  • Neuropeptides / metabolism
  • Receptors, Cell Surface / metabolism*
  • Receptors, Neurotransmitter*
  • Sequence Analysis, Protein


  • Ligands
  • Membrane Proteins
  • Neuropeptides
  • Receptors, Cell Surface
  • Receptors, Neurotransmitter
  • neuromedin U receptor
  • neuromedin U