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Identification of receptors for neuromedin U and its role in feeding

Nature volume 406, pages 70–74 (2000)Cite this article

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.

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Figure 1: Sequence comparison of FM-3 and FM-4.
Figure 2: Functional and binding analysis.
Figure 3: Expression of NMU1R and NMU2R.
Figure 4: In situ hybridization analysis of NMU in the rat brain.
Figure 5: Effect of ICV-administrated NMU in rats.

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Acknowledgements

We thank M. Abramowitz and R. Stocco of Merck Frosst Canada for setting up the aequorin assay.

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Author notes

  1. C. Thomas Caskey

    Present address: Cogene Biotech Ventures, 711 Louisiana Street, Ste 3350, Houston, Texas, 77002, USA

  2. Andrew D. Howard, Ruiping Wang and C. Thomas Caskey: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Metabolic Disorders and,

    Andrew D. Howard, Sheng-Shung Pong, Xiao-Ming Guan, Scott D. Feighner, Hong Yu, Carina P. Tan, Karen K. McKee, Donna L. Hreniuk & Lex H. T. Van der Ploeg

  2. Department of Animal Pharmacology, Merck Research Laboratories, PO Box 2000, Rahway, 07065, New Jersey, USA

    Theodore N. Mellin, Alison Strack, Christian N. Nunes, Beth Murphy & Judith N. Stair

  3. Department of Pharmacology,,

    Ruiping Wang, Zhizhen Zeng, David L. Williams Jr, Qingping Jiang, Michelle K. Clements, Terrence P. McDonald, Jilly F. Evans, Christopher P. Austin & Qingyun Liu

  4. Merck Research Laboratories, West Point, 19486, Pennsylvania, USA

    Kevin R. Lynch

  5. Department of Pharmacology, University of Virginia Health Sciences Center, Charlottesville, 22908, Virginia, USA

    C. Thomas Caskey

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Correspondence to Qingyun Liu.

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Howard, A., Wang, R., Pong, SS. et al. Identification of receptors for neuromedin U and its role in feeding . Nature 406, 70–74 (2000). https://doi.org/10.1038/35017610

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