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Identification of receptors for neuromedin U and its role in feeding

Author

Listed:
  • Andrew D. Howard

    (Department of Metabolic Disorders and)

  • Ruiping Wang

    (Department of Pharmacology,)

  • Sheng-Shung Pong

    (Department of Metabolic Disorders and)

  • Theodore N. Mellin

    (Merck Research Laboratories)

  • Alison Strack

    (Merck Research Laboratories)

  • Xiao-Ming Guan

    (Department of Metabolic Disorders and)

  • Zhizhen Zeng

    (Department of Pharmacology,)

  • David L. Williams

    (Department of Pharmacology,)

  • Scott D. Feighner

    (Department of Metabolic Disorders and)

  • Christian N. Nunes

    (Merck Research Laboratories)

  • Beth Murphy

    (Merck Research Laboratories)

  • Judith N. Stair

    (Merck Research Laboratories)

  • Hong Yu

    (Department of Metabolic Disorders and)

  • Qingping Jiang

    (Department of Pharmacology,)

  • Michelle K. Clements

    (Department of Pharmacology,)

  • Carina P. Tan

    (Department of Metabolic Disorders and)

  • Karen K. McKee

    (Department of Metabolic Disorders and)

  • Donna L. Hreniuk

    (Department of Metabolic Disorders and)

  • Terrence P. McDonald

    (Department of Pharmacology,)

  • Kevin R. Lynch

    (Merck Research Laboratories)

  • Jilly F. Evans

    (Department of Pharmacology,)

  • Christopher P. Austin

    (Department of Pharmacology,)

  • C. Thomas Caskey

    (University of Virginia Health Sciences Center
    Cogene Biotech Ventures)

  • Lex H. T. Van der Ploeg

    (Department of Metabolic Disorders and)

  • Qingyun Liu

    (Department of Pharmacology,)

Abstract

Neuromedin U (NMU) is a neuropeptide with potent activity on smooth muscle which was isolated first from porcine spinal cord and later from other species1,2,3,4,5,6,7,8. It is widely distributed in the gut and central nervous system9,10. Peripheral activities of NMU include stimulation of smooth muscle1, increase of blood pressure1, alteration of ion transport in the gut11, control of local blood flow12,13 and regulation of adrenocortical function14. An NMU receptor has not been molecularly identified. Here we show that the previously described orphan G-protein-coupled receptor FM-3 (ref. 15) and a newly discovered one (FM-4) are cognate receptors for NMU. FM-3, designated NMU1R, is abundantly expressed in peripheral tissues whereas FM-4, designated NMU2R, is expressed in specific regions of the brain. NMU is expressed in the ventromedial hypothalamus in the rat brain, and its level is significantly reduced following fasting. Intracerebroventricular administration of NMU markedly suppresses food intake in rats. These findings provide a molecular basis for the biochemical activities of NMU and may indicate that NMU is involved in the central control of feeding.

Suggested Citation

  • Andrew D. Howard & Ruiping Wang & Sheng-Shung Pong & Theodore N. Mellin & Alison Strack & Xiao-Ming Guan & Zhizhen Zeng & David L. Williams & Scott D. Feighner & Christian N. Nunes & Beth Murphy & Jud, 2000. "Identification of receptors for neuromedin U and its role in feeding," Nature, Nature, vol. 406(6791), pages 70-74, July.
    • Handle: RePEc:nat:nature:v:406:y:2000:i:6791:d:10.1038_35017610
    DOI: 10.1038/35017610
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    Cited by:

    1. Wenli Zhao & Wenru Zhang & Mu Wang & Minmin Lu & Shutian Chen & Tingting Tang & Gisela Schnapp & Holger Wagner & Albert Brennauer & Cuiying Yi & Xiaojing Chu & Shuo Han & Beili Wu & Qiang Zhao, 2022. "Ligand recognition and activation of neuromedin U receptor 2," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    2. Sayaka Aizawa & Ichiro Sakata & Mai Nagasaka & Yuriko Higaki & Takafumi Sakai, 2013. "Negative Regulation of Neuromedin U mRNA Expression in the Rat Pars Tuberalis by Melatonin," PLOS ONE, Public Library of Science, vol. 8(7), pages 1-9, July.
    3. Chongzhao You & Yumu Zhang & Peiyu Xu & Sijie Huang & Wanchao Yin & H. Eric Xu & Yi Jiang, 2022. "Structural insights into the peptide selectivity and activation of human neuromedin U receptors," Nature Communications, Nature, vol. 13(1), pages 1-10, December.

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