Identification of a Human Gastrointestinal Tract and Immune System Receptor for the Peptide Neuromedin U
| Autor: | Xudong Qiao, Ling Pang, Suke Wang, Joseph A. Hedrick, Frederick J. Monsma, Kelley L. Morse, Thomas M. Laz, LiXin Shan, Marvin L. Bayne, Eric L. Gustafson |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
medicine.medical_specialty
T-Lymphocytes Molecular Sequence Data Receptors Cell Surface Biology Transfection Calcium in biology Neuromedin U receptor Immune system Internal medicine Calcium flux medicine Humans Amino Acid Sequence RNA Messenger Cloning Molecular Receptor Cells Cultured Pharmacology Dose-Response Relationship Drug Sequence Homology Amino Acid Neuropeptides Membrane Proteins Smooth muscle contraction Receptors Neurotransmitter Cell biology Killer Cells Natural Endocrinology Molecular Medicine Calcium Neuromedin S Digestive System Neuromedin U |
| Zdroj: | Molecular Pharmacology. 58:870-875 |
| ISSN: | 1521-0111 0026-895X |
| DOI: | 10.1124/mol.58.4.870 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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