Abstract：
: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 (EC(50) = 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.
journal_name
Mol Pharmacoljournal_title
Molecular pharmacologyauthors
Hedrick JA,Morse K,Shan L,Qiao X,Pang L,Wang S,Laz T,Gustafson EL,Bayne M,Monsma FJ Jrdoi
10.1124/mol.58.4.870keywords:
subject
Has Abstractpub_date
2000-10-01 00:00:00pages
870-5issue
4eissn
0026-895Xissn
1521-0111journal_volume
58pub_type
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