Document Detail


Increases in guanylin and uroguanylin in a mouse model of osmotic diarrhea are guanylate cyclase C-independent.
MedLine Citation:
PMID:  11677212     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND & AIMS: Guanylin and uroguanylin are peptide hormones that are homologous to the diarrhea-causing Escherichia coli enterotoxins. These secretagogues are released from the intestinal epithelia into the intestinal lumen and systemic circulation and bind to the receptor guanylate cyclase C (GC-C). We hypothesized that a hypertonic diet would result in osmotic diarrhea and cause a compensatory down-regulation of guanylin/uroguanylin. METHODS: Gut-to-carcass weights were used to measure fluid accumulation in the intestine. Northern and/or Western analysis was used to determine the levels of guanylin, uroguanylin, and GC-C in mice with osmotic diarrhea. RESULTS: Wild-type mice fed a polyethylene glycol or lactose-based diet developed weight loss, diarrhea, and an increased gut-to-carcass ratio. Unexpectedly, 2 days on either diet resulted in increased guanylin/uroguanylin RNA and prohormone throughout the intestine, elevated uroguanylin RNA, and prohormone levels in the kidney and increased levels of circulating prouroguanylin. GC-C-deficient mice given the lactose diet reacted with higher gut-to-carcass ratios. Although they did not develop diarrhea, GC-C-sufficient and -deficient mice on the lactose diet responded with elevated levels of guanylin and uroguanylin RNA and protein. A polyethylene glycol drinking water solution resulted in diarrhea, higher gut-to-carcass ratios, and induction of guanylin and uroguanylin in both GC-C heterozygous and null animals. CONCLUSIONS: We conclude that this model of osmotic diarrhea results in a GC-C-independent increase in intestinal fluid accumulation, in levels of these peptide ligands in the epithelia of the intestine, and in prouroguanylin in the kidney and blood.
Authors:
K A Steinbrecher; E A Mann; R A Giannella; M B Cohen
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Gastroenterology     Volume:  121     ISSN:  0016-5085     ISO Abbreviation:  Gastroenterology     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-10-25     Completed Date:  2001-12-05     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0374630     Medline TA:  Gastroenterology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1191-202     Citation Subset:  AIM; IM    
Affiliation:
Division of Pediatric Gastroenterology, Hepatology and Nutrition and Graduate Program in Molecular and Developmental Biology, Children's Hospital Research Foundation, Cincinnati, Ohio, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antiporters*
Carrier Proteins / genetics
Diarrhea / metabolism*
Female
Gastrointestinal Hormones*
Guanylate Cyclase*
Intestines / metabolism
Kidney / metabolism
Membrane Proteins / genetics
Mice
Mice, Inbred C57BL
Natriuretic Peptides
Osmotic Pressure
Peptides / analysis*,  genetics,  physiology
RNA, Messenger / analysis
Receptors, Cell Surface / physiology*
Receptors, Peptide*
Sodium-Hydrogen Antiporter / genetics
Grant Support
ID/Acronym/Agency:
DK 47318/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Antiporters; 0/Carrier Proteins; 0/Gastrointestinal Hormones; 0/Membrane Proteins; 0/Natriuretic Peptides; 0/Peptides; 0/RNA, Messenger; 0/Receptors, Cell Surface; 0/Receptors, Peptide; 0/Slc26a3 protein, mouse; 0/Sodium-Hydrogen Antiporter; 0/sodium-hydrogen exchanger 3; 140653-38-9/guanylin; 152175-68-3/uroguanylin; EC 4.6.1.2/Guanylate Cyclase; EC 4.6.1.2/enterotoxin receptor

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


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