Normal mouse intestinal mucus release requires cystic fibrosis transmembrane regulator–dependent bicarbonate secretion
Open Access
- 1 September 2009
- journal article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 119 (9), 2613-2622
- https://doi.org/10.1172/jci38662
Abstract
The mechanisms underlying mucus-associated pathologies in cystic fibrosis (CF) remain obscure. However, recent studies indicate that CF transmembrane conductance regulator (CFTR) is required for bicarbonate (HCO3–) transport and that HCO3– is critical for normal mucus formation. We therefore investigated the role of HCO3– in mucus secretion using mouse small intestine segments ex vivo. Basal rates of mucus release in the presence or absence of HCO3– were similar. However, in the absence of HCO3–, mucus release stimulated by either PGE2 or 5-hydroxytryptamine (5-HT) was approximately half that stimulated by these molecules in the presence of HCO3–. Inhibition of HCO3– and fluid transport markedly reduced stimulated mucus release. However, neither absence of HCO3– nor inhibition of HCO3– transport affected fluid secretion rates, indicating that the effect of HCO3– removal on mucus release was not due to decreased fluid secretion. In a mouse model of CF (mice homozygous for the most common human CFTR mutation), intestinal mucus release was minimal when stimulated with either PGE2 or 5-HT in the presence or absence of HCO3–. These data suggest that normal mucus release requires concurrent HCO3– secretion and that the characteristically aggregated mucus observed in mucin-secreting organs in individuals with CF may be a consequence of defective HCO3– transport.This publication has 64 references indexed in Scilit:
- The inner of the two Muc2 mucin-dependent mucus layers in colon is devoid of bacteriaProceedings of the National Academy of Sciences of the United States of America, 2008
- Liquid movement across the surface epithelium of large airwaysRespiratory Physiology & Neurobiology, 2007
- Absence of CFTR is associated with pleiotropic effects on mucins in mouse gallbladder epithelial cellsAmerican Journal of Physiology-Gastrointestinal and Liver Physiology, 2006
- Slc26a6 regulates CFTR activity in vivo to determine pancreatic duct HCO3− secretion: relevance to cystic fibrosisThe EMBO Journal, 2006
- Control of dynamic CFTR selectivity by glutamate and ATP in epithelial cellsNature, 2003
- Intestinal mucins from cystic fibrosis mice show increased fucosylation due to an induced Fucα1-2 glycosyltransferaseBiochemical Journal, 2002
- Mucus Secretion from Single Submucosal Glands of PigOnline Journal of Public Health Informatics, 2002
- Cellular localization of cystic fibrosis transmembrane regulator protein in piglet and mouse intestineCell and tissue research, 1996
- Calcium and Phosphorus Levels in Submaxillary SalivaClinical Pediatrics, 1969
- SOME ACHIEVEMENTS AND PROBLEMS IN STUDYING THE SOLUBILITY OF THE MINERAL OF THE HARD TISSUESAnnals of the New York Academy of Sciences, 1955