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https://hdl.handle.net/2440/75924
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Type: | Journal article |
Title: | Guanylate cyclase-C receptor activation: unexpected biology |
Author: | Brierley, S. |
Citation: | Current Opinion in Pharmacology, 2012; 12(6):632-640 |
Publisher: | Elsevier Science Ltd |
Issue Date: | 2012 |
ISSN: | 1471-4892 1471-4973 |
Statement of Responsibility: | Stuart M Brierley |
Abstract: | Guanylate cyclase-C (GC-C) is a transmembrane receptor activated by bacterial heat-stable enterotoxins and by the endogenous hormones guanylin and uroguanylin. GC-C plays key roles in the regulation of intestinal fluid and electrolyte homeostasis. This is highlighted by several recently identified human mutations in GUCY2C, the gene encoding GC-C, which leads to the respective gain or loss of function of GC-C, resulting in profound effects on gastrointestinal function. However, a wealth of recent studies indicates GC-C signalling extends to a multitude of diverse additional functions. Recent pre-clinical and clinical studies demonstrate a novel first-in-class GC-C activating peptide, Linaclotide, provides effective relief from constipation and abdominal pain in patients with chronic constipation and constipation-predominant Irritable Bowel Syndrome. Accumulating evidence also suggests GC-C plays protective roles in mucosal barrier function, tissue injury and inflammation, whilst GC-C signalling is a key regulator of intestinal cell proliferation and apoptosis. Finally, recently identified extra-intestinal GC-C signalling pathways make novel contributions to the regulation of food intake and symptoms associated with Attention Deficit Hyperactivity Disorder. Consequently, these findings provide GC-C expression and its associated mutations as potential diagnostic markers for disease. They also provide current and future therapeutic potential for GC-C signalling within and outside the gastrointestinal tract. |
Keywords: | Gastrointestinal Tract Intestinal Secretions Animals Humans Gastrointestinal Diseases Electrolytes Peptides Receptors, Peptide Signal Transduction Apoptosis Cell Proliferation Gene Expression Mutation Receptors, Guanylate Cyclase-Coupled Receptors, Enterotoxin |
Rights: | Crown copyright © 2012. All rights reserved. |
DOI: | 10.1016/j.coph.2012.10.005 |
Published version: | http://dx.doi.org/10.1016/j.coph.2012.10.005 |
Appears in Collections: | Aurora harvest 4 Molecular and Biomedical Science publications |
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