RT Journal Article
SR Electronic
T1 Identification of a Human Gastrointestinal Tract and Immune System Receptor for the Peptide Neuromedin U
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 870
OP 875
DO 10.1124/mol.58.4.870
VO 58
IS 4
A1 Joseph A. Hedrick
A1 Kelley Morse
A1 LiXin Shan
A1 Xudong Qiao
A1 Ling Pang
A1 Suke Wang
A1 Thomas Laz
A1 Eric L. Gustafson
A1 Marvin Bayne
A1 Frederick J. Monsma, Jr.
YR 2000
UL http://molpharm.aspetjournals.org/content/58/4/870.abstract
AB 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.