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Guanylate cyclase-C as a therapeutic target in gastrointestinal disorders
Functional gastrointestinal disorders (FGIDs) and IBDs are two of the most prevalent disorders of the GI tract and consume a significant proportion of healthcare resources. Recent studies have shown that membrane-bound guanylate cyclase-C (GC-C) receptors lining the GI tract may serve as novel thera...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BMJ Publishing Group
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6204952/ https://www.ncbi.nlm.nih.gov/pubmed/29563144 http://dx.doi.org/10.1136/gutjnl-2018-316029 |
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author | Waldman, Scott A Camilleri, Michael |
author_facet | Waldman, Scott A Camilleri, Michael |
author_sort | Waldman, Scott A |
collection | PubMed |
description | Functional gastrointestinal disorders (FGIDs) and IBDs are two of the most prevalent disorders of the GI tract and consume a significant proportion of healthcare resources. Recent studies have shown that membrane-bound guanylate cyclase-C (GC-C) receptors lining the GI tract may serve as novel therapeutic targets in the treatment of FGIDs and IBDs. GC-C receptor activation by its endogenous paracrine hormones uroguanylin and guanylin, and the resulting intracellular production of its downstream effector cyclic GMP, occurs in a pH-dependent manner and modulates key physiological functions. These include fluid and electrolyte homeostasis, maintenance of the intestinal barrier, anti-inflammatory activity and regulation of epithelial regeneration. Studies of the GC-C paracrine signalling axis have revealed the therapeutic potential of these receptors in treating GI disorders, including chronic idiopathic constipation and irritable bowel syndrome–constipation. This review focuses on the evolving understanding of GC-C function in health and disease, and strategies for translating these principles into new treatments for FGIDs and IBDs. |
format | Online Article Text |
id | pubmed-6204952 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-62049522018-11-08 Guanylate cyclase-C as a therapeutic target in gastrointestinal disorders Waldman, Scott A Camilleri, Michael Gut Recent Advances in Clinical Practice Functional gastrointestinal disorders (FGIDs) and IBDs are two of the most prevalent disorders of the GI tract and consume a significant proportion of healthcare resources. Recent studies have shown that membrane-bound guanylate cyclase-C (GC-C) receptors lining the GI tract may serve as novel therapeutic targets in the treatment of FGIDs and IBDs. GC-C receptor activation by its endogenous paracrine hormones uroguanylin and guanylin, and the resulting intracellular production of its downstream effector cyclic GMP, occurs in a pH-dependent manner and modulates key physiological functions. These include fluid and electrolyte homeostasis, maintenance of the intestinal barrier, anti-inflammatory activity and regulation of epithelial regeneration. Studies of the GC-C paracrine signalling axis have revealed the therapeutic potential of these receptors in treating GI disorders, including chronic idiopathic constipation and irritable bowel syndrome–constipation. This review focuses on the evolving understanding of GC-C function in health and disease, and strategies for translating these principles into new treatments for FGIDs and IBDs. BMJ Publishing Group 2018-08 2018-03-21 /pmc/articles/PMC6204952/ /pubmed/29563144 http://dx.doi.org/10.1136/gutjnl-2018-316029 Text en © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted. This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ |
spellingShingle | Recent Advances in Clinical Practice Waldman, Scott A Camilleri, Michael Guanylate cyclase-C as a therapeutic target in gastrointestinal disorders |
title | Guanylate cyclase-C as a therapeutic target in gastrointestinal disorders |
title_full | Guanylate cyclase-C as a therapeutic target in gastrointestinal disorders |
title_fullStr | Guanylate cyclase-C as a therapeutic target in gastrointestinal disorders |
title_full_unstemmed | Guanylate cyclase-C as a therapeutic target in gastrointestinal disorders |
title_short | Guanylate cyclase-C as a therapeutic target in gastrointestinal disorders |
title_sort | guanylate cyclase-c as a therapeutic target in gastrointestinal disorders |
topic | Recent Advances in Clinical Practice |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6204952/ https://www.ncbi.nlm.nih.gov/pubmed/29563144 http://dx.doi.org/10.1136/gutjnl-2018-316029 |
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