Identification of a Human Gastrointestinal Tract and Immune System Receptor for the Peptide Neuromedin U
- Joseph A. Hedrick,
- Kelley Morse,
- LiXin Shan,
- Xudong Qiao,
- Ling Pang,
- Suke Wang,
- Thomas Laz,
- Eric L. Gustafson,
- Marvin Bayne and
- Frederick J. Monsma, Jr.
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 (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.
Footnotes
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Send reprint requests to: Joseph A. Hedrick, Ph.D., Schering-Plough Research Institute, 2015 Galloping Hill Rd., K-15-1/1945, Kenilworth, NJ 07033-1300. E-mail:joseph.hedrick{at}spcorp.com
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This research was funded entirely by Schering-Plough Corporation.
- Abbreviations:
- Nm
- neuromedin
- GI
- gastrointestinal
- GPCR
- G protein-coupled receptor
- TM
- transmembrane
- PCR
- polymerase chain reaction
- DMEM
- Dulbecco's modified Eagle's medium
- FCS
- fetal calf serum
- bp
- base pair(s)
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- Received June 14, 2000.
- Accepted July 14, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
