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Research ArticleArticle

Neuromedin U and Its Receptors: Structure, Function, and Physiological Roles

Paul J. Brighton, Philip G. Szekeres and Gary B. Willars
Pharmacological Reviews June 2004, 56 (2) 231-248; DOI: https://doi.org/10.1124/pr.56.2.3
Paul J. Brighton
Department of Cell Physiology and Pharmacology, University of Leicester, Leicester, United Kingdom (P.J.B., G.B.W.); and GlaxoSmithKline, Harlow, United Kingdom (P.G.S.)
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Philip G. Szekeres
Department of Cell Physiology and Pharmacology, University of Leicester, Leicester, United Kingdom (P.J.B., G.B.W.); and GlaxoSmithKline, Harlow, United Kingdom (P.G.S.)
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Gary B. Willars
Department of Cell Physiology and Pharmacology, University of Leicester, Leicester, United Kingdom (P.J.B., G.B.W.); and GlaxoSmithKline, Harlow, United Kingdom (P.G.S.)
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Abstract

Neuromedin U (NmU) is a structurally highly conserved neuropeptide. It is ubiquitously distributed, with highest levels found in the gastrointestinal tract and pituitary. Originally isolated from porcine spinal cord, it has since been isolated and sequenced from several species. Amino acid alignment of NmU from different species reveals a high level of conservation, and particular features within its structure are important for bioactivity. Specifically, the C terminus, including a terminal asparagine-linked amidation, is essential for activity. The conservation of NmU across a wide range of species indicates a strong evolutionary pressure to conserve this peptide and points to its physiological significance. Despite this, the precise physiological and indeed pathophysiological roles of NmU have remained elusive. NmU was first isolated based on its ability to contract rat uterine smooth-muscle (hence the suffix “U”) and has since been implicated inthe regulation of smooth-muscle contraction, blood pressure and local blood flow, ion transport in the gut, stress responses, cancer, gastric acid secretion, pronociception, and feeding behavior. Two G-protein-coupled receptors for NmU have recently been cloned. These receptors are widespread throughout the body but have differential distributions suggesting diverse but specific roles for the receptor subtypes. Here we detail the isolation and characterization of NmU, describe the discovery, cloning, distribution, and structure of its two receptors, and outline its possible roles in both physiology and pathophysiology. Ultimately the development of receptor-specific ligands and the generation of animals in which the receptors have been selectively knocked out will hopefully reveal the true extent of the biological roles of NmU and suggest novel therapeutic indications for selective activation or blockade of either of its receptors.

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Pharmacological Reviews: 56 (2)
Pharmacological Reviews
Vol. 56, Issue 2
1 Jun 2004
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Research ArticleArticle

Neuromedin U and Its Receptors: Structure, Function, and Physiological Roles

Paul J. Brighton, Philip G. Szekeres and Gary B. Willars
Pharmacological Reviews June 1, 2004, 56 (2) 231-248; DOI: https://doi.org/10.1124/pr.56.2.3

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Research ArticleArticle

Neuromedin U and Its Receptors: Structure, Function, and Physiological Roles

Paul J. Brighton, Philip G. Szekeres and Gary B. Willars
Pharmacological Reviews June 1, 2004, 56 (2) 231-248; DOI: https://doi.org/10.1124/pr.56.2.3
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  • Article
    • Abstract
    • I. Discovery, Isolation, Structure, and Synthesis of Neuromedin U
    • II. Structure-Activity Relationships of Neuromedin U
    • III. Regional, Cellular, and Subcellular Distribution of Neuromedin U
    • IV. Receptors for Neuromedin U
    • V. Physiological Roles of Neuromedin U
    • VI. Summary
    • Acknowledgments
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