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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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Autores principales: Waldman, Scott A, Camilleri, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2018
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.
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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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