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

Kojima M., Haruno R., Nakazato M., Date Y., Murakami N., Hanada R., Matsuo H., Kangawa K.

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.

Biochem. Biophys. Res. Commun. 276:435-438(2000) [PubMed] [Europe PMC]

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