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Rapid CommunicationAccelerated Communication

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
Molecular Pharmacology October 2000, 58 (4) 870-875; DOI: https://doi.org/10.1124/mol.58.4.870
Joseph A. Hedrick
Human Genome Research, Schering-Plough Research Institute, Kenilworth, New Jersey
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Kelley Morse
Human Genome Research, Schering-Plough Research Institute, Kenilworth, New Jersey
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LiXin Shan
Human Genome Research, Schering-Plough Research Institute, Kenilworth, New Jersey
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Xudong Qiao
Human Genome Research, Schering-Plough Research Institute, Kenilworth, New Jersey
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Ling Pang
Human Genome Research, Schering-Plough Research Institute, Kenilworth, New Jersey
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Suke Wang
Human Genome Research, Schering-Plough Research Institute, Kenilworth, New Jersey
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Thomas Laz
Human Genome Research, Schering-Plough Research Institute, Kenilworth, New Jersey
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Eric L. Gustafson
Human Genome Research, Schering-Plough Research Institute, Kenilworth, New Jersey
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Marvin Bayne
Human Genome Research, Schering-Plough Research Institute, Kenilworth, New Jersey
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Frederick J. Monsma
Human Genome Research, Schering-Plough Research Institute, Kenilworth, New Jersey
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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

    • Received June 14, 2000.
    • Accepted July 14, 2000.
  • 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

  • This research was funded entirely by Schering-Plough Corporation.

  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 58 (4)
Molecular Pharmacology
Vol. 58, Issue 4
1 Oct 2000
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Rapid CommunicationAccelerated Communication

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
Molecular Pharmacology October 1, 2000, 58 (4) 870-875; DOI: https://doi.org/10.1124/mol.58.4.870

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Rapid CommunicationAccelerated Communication

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
Molecular Pharmacology October 1, 2000, 58 (4) 870-875; DOI: https://doi.org/10.1124/mol.58.4.870
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