TY - JOUR T1 - Identification of a Human Gastrointestinal Tract and Immune System Receptor for the Peptide Neuromedin U JF - Molecular Pharmacology JO - Mol Pharmacol SP - 870 LP - 875 DO - 10.1124/mol.58.4.870 VL - 58 IS - 4 AU - Joseph A. Hedrick AU - Kelley Morse AU - LiXin Shan AU - Xudong Qiao AU - Ling Pang AU - Suke Wang AU - Thomas Laz AU - Eric L. Gustafson AU - Marvin Bayne AU - Frederick J. Monsma, Jr. Y1 - 2000/10/01 UR - http://molpharm.aspetjournals.org/content/58/4/870.abstract N2 - 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. ER -