Journal
JOURNAL OF CLINICAL INVESTIGATION
Volume 119, Issue 9, Pages 2613-2622Publisher
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI38662
Keywords
-
Categories
Funding
- Nancy Olmted Trust [NIH-NHLB RO1-HL084042]
- Cystic Fibrosis Foundation
- NIH [MO1 IZR-00827]
Ask authors/readers for more resources
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 PGE(2) 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available