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J Clin Invest. 2009 Sep;119(9):2613-22. doi: 10.1172/JCI38662. Epub 2009 Aug 24.

Normal mouse intestinal mucus release requires cystic fibrosis transmembrane regulator-dependent bicarbonate secretion.

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  • 1Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of California School of Medicine, San Diego, California 92093-0831, USA.

Erratum in

  • J Clin Invest. 2009 Nov;119(11):3497.

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.

Comment in

PMID:
19726884
[PubMed - indexed for MEDLINE]
PMCID:
PMC2735925
Free PMC Article

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