| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Article |
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.)
Abstract
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 A. Central Nervous System B. Peripheral Distribution IV. Receptors for Neuromedin U A. Discovery B. Characterization of Neuromedin U-R1 and Neuromedin U-R2 C. Tissue Distribution of Neuromedin U-R1 and Neuromedin U-R2 D. Regulation of Cellular Signaling Pathways by Neuromedin U V. Physiological Roles of Neuromedin U A. Smooth-Muscle Contraction B. Blood Pressure and Regional Blood Flow C. Hypothalamo-Pituitary-Adrenal Axis and the Stress Response D. Feeding and Energy Homeostasis E. Gastric Acid Secretion and Gastric Emptying F. Effects on Ion Transport G. Cancer H. Pronociception I. Immune Regulation VI. Summary
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.
This article has been cited by other articles:
|
|
 |
|
  C. Galasso, A. Lo-Castro, C. Lalli, A. M. Nardone, F. Gullotta, and P. Curatolo Deletion 2q37: An Identifiable Clinical Syndrome With Mental Retardation and Autism J Child Neurol, July 1, 2008; 23(7): 802 - 806. [Abstract] [PDF]
|
|
|
|
 |
|
 P. J. Brighton, A. Wise, N. B. Dass, and G. B. Willars Paradoxical Behavior of Neuromedin U in Isolated Smooth Muscle Cells and Intact Tissue J. Pharmacol. Exp. Ther., April 1, 2008; 325(1): 154 - 164. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Vigo, J. Roa, R. Pineda, J. M. Castellano, V. M. Navarro, E. Aguilar, L. Pinilla, and M. Tena-Sempere Novel role of the anorexigenic peptide neuromedin U in the control of LH secretion and its regulation by gonadal hormones and photoperiod Am J Physiol Endocrinol Metab, November 1, 2007; 293(5): E1265 - E1273. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-H. Hsu and C.-W. Luo Molecular dissection of G protein preference using Gs{alpha} chimeras reveals novel ligand signaling of GPCRs Am J Physiol Endocrinol Metab, October 1, 2007; 293(4): E1021 - E1029. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Zeng, A. Gragerov, J. G. Hohmann, M. N. Pavlova, B. A. Schimpf, H. Xu, L.-J. Wu, H. Toyoda, M.-G. Zhao, A. D. Rohde, et al. Neuromedin U Receptor 2-Deficient Mice Display Differential Responses in Sensory Perception, Stress, and Feeding Mol. Cell. Biol., December 15, 2006; 26(24): 9352 - 9363. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Wettschureck and S. Offermanns Mammalian G Proteins and Their Cell Type Specific Functions Physiol Rev, October 1, 2005; 85(4): 1159 - 1204. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T J Kowalski, B D Spar, L Markowitz, M Maguire, A Golovko, S Yang, C Farley, J A Cook, G Tetzloff, L Hoos, et al. Transgenic overexpression of neuromedin U promotes leanness and hypophagia in mice J. Endocrinol., April 1, 2005; 185(1): 151 - 164. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Holst, N. D. Holliday, A. Bach, C. E. Elling, H. M. Cox, and T. W. Schwartz Common Structural Basis for Constitutive Activity of the Ghrelin Receptor Family J. Biol. Chem., December 17, 2004; 279(51): 53806 - 53817. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Hull, A. Ohnishi, K. Moto, Y. Kawasaki, R. Kurata, M. G. Suzuki, and S. Matsumoto Cloning and Characterization of the Pheromone Biosynthesis Activating Neuropeptide Receptor from the Silkmoth, Bombyx mori: SIGNIFICANCE OF THE CARBOXYL TERMINUS IN RECEPTOR INTERNALIZATION J. Biol. Chem., December 3, 2004; 279(49): 51500 - 51507. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. J. Brighton, P. G. Szekeres, A. Wise, and G. B. Willars Signaling and Ligand Binding by Recombinant Neuromedin U Receptors: Evidence for Dual Coupling to G{alpha}q/11 and G{alpha}i and an Irreversible Ligand-Receptor Interaction Mol. Pharmacol., December 1, 2004; 66(6): 1544 - 1556. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
 |
 |
 |
|
 |
 |
 |
