Document Detail


The multiple roles of guanylate cyclase C, a heat stable enterotoxin receptor.
MedLine Citation:
PMID:  24304979     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE OF REVIEW: Guanylate cyclase C (GC-C) is a transmembrane receptor that is expressed primarily on intestinal epithelial cells. Activation of this receptor by its endogenous peptide ligands initiates cyclic guanosine monophosphate-dependent (cGMP) salt and water movement in the intestine. GC-C is targeted by the enterotoxigenic Escherichia coli heat-stable enterotoxin STa, which deregulates this pathway and causes secretory diarrhea. This review discusses current work on the physiological function of GC-C in the intestine.
RECENT FINDINGS: Familial GC-C mutations demonstrate that epithelial cGMP signaling is critical to electrolyte and fluid balance in the neonatal intestine. Chronic deregulation of GC-C activity in early life increases susceptibility to a number of disorders, including obstruction and inflammatory bowel disease. Murine models indicate that GC-C regulates the composition of intestinal commensal microflora and that it suppresses bacterial infection and modulates colonic injury and inflammation. Therapeutic GC-C ligands are used to successfully treat constipation-predominant irritable bowel syndrome and recent studies show that extracellular cGMP is an important mechanism of reducing abdominal pain associated with this disorder.
SUMMARY: Originally identified as a target of E. coli enterotoxin STa, GC-C is an important regulator of physiological salt and water homeostasis and may directly impact a wide range of intestinal disorders.
Authors:
Kris A Steinbrecher
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Review    
Journal Detail:
Title:  Current opinion in gastroenterology     Volume:  30     ISSN:  1531-7056     ISO Abbreviation:  Curr. Opin. Gastroenterol.     Publication Date:  2014 Jan 
Date Detail:
Created Date:  2013-12-05     Completed Date:  2014-07-01     Revised Date:  2014-07-02    
Medline Journal Info:
Nlm Unique ID:  8506887     Medline TA:  Curr Opin Gastroenterol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1-6     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adhesins, Bacterial / physiology
Homeostasis / physiology
Humans
Inflammatory Bowel Diseases / enzymology*
Intestinal Absorption / physiology
Intestines / microbiology
Irritable Bowel Syndrome / drug therapy,  enzymology*
Receptors, Atrial Natriuretic Factor / agonists,  physiology*
Signal Transduction / physiology
Water-Electrolyte Balance / physiology
Grant Support
ID/Acronym/Agency:
AI107274/AI/NIAID NIH HHS; DK047318/DK/NIDDK NIH HHS; R21 AI107274/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Adhesins, Bacterial; EC 4.6.1.2/Receptors, Atrial Natriuretic Factor; EC 4.6.1.2/atrial natriuretic factor receptor C

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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