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Vol. 58, Issue 4, 870-875, October 2000
Human Genome Research, Schering-Plough Research Institute,
Kenilworth, New Jersey
Neuromedin U (NmU) is a 25 amino acid peptide prominently expressed in
the upper gastrointestinal (GI) tract and central nervous system. It is
highly conserved throughout evolution and induces smooth muscle
contraction in a variety of species. Our understanding of NmU biology
has been limited because the identity of its receptor was unknown. Here
we demonstrate that GPR66/FM-3 is specifically stimulated by NmU,
causing the mobilization of intracellular calcium. This response was
dose-dependent (EC50 = 10 nM) and specific in
that none of over 1000 ligands tested, including other neuromedins (NmB, C, L, K, N), induced a calcium flux in GPR66/FM-3-transfected cells. The GPR66/FM-3 mRNA is prominently expressed in the upper GI
tract of humans, as is the mRNA for NmU, consistent with role for this
receptor-ligand pair in regulating the function of this organ system.
In addition, we show that whereas neuromedin U is expressed by
monocytes and dendritic cells, GPR66/FM-3 is expressed by T cells and
NK cells. These data suggest a previously unrecognized role for NmU as
an immunoregulatory molecule.
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