Coupled secretion of chloride and mucus in skin of Xenopus laevis: possible role for CFTR

We used the isolated skin of Xenopus laevis to investigate the relationship between the secretion of salt, water, and mucus by submucosal glands expressing the cystic fibrosis transmembrane conductance regulator (CFTR). In situ hybridization and immunofluorescence provided evidence for specific expression of CFTR in the mucus-secreting cells of the subepidermal glands. Stimulation of isolated sheets of skin with 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate produced active Cl secretion and a marked increase in tissue conductance that was correlated with mucous cell degranulation and the distention of the glandular ducts. This coordinated increase in active secretion of salt and mucus was abolished by pretreatment of skins with bumetanide or by removing Cl from the bathing solutions. These results provide evidence for an intimate coupling between electrolyte transport and mucus secretion that may illuminate the pathophysiology of mucus-producing glands in cystic fibrosis lung disease.

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Enhancement of alveolar epithelial sodium channel activity with decreased cystic fibrosis transmembrane conductance regulator expression in mouse lung

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00094.2011 ◽

2011 ◽

Vol 301 (4) ◽

pp. L557-L567 ◽

Cited By ~ 37

Author(s):

Ahmed Lazrak ◽

Asta Jurkuvenaite ◽

Lan Chen ◽

Kim M. Keeling ◽

James F. Collawn ◽

...

Keyword(s):

Cystic Fibrosis ◽

Epithelial Cells ◽

Alveolar Epithelial Cells ◽

Alveolar Type ◽

Transmembrane Conductance Regulator ◽

Wild Type ◽

Transmembrane Conductance ◽

Alveolar Epithelial ◽

Cystic Fibrosis Transmembrane

We sought to establish whether the cystic fibrosis transmembrane conductance regulator (CFTR) regulates the activity of amiloride-sensitive sodium channels (ENaC) in alveolar epithelial cells of wild-type, heterozygous ( Cftr +/−), knockout ( Cftr −/−), and ΔF508-expressing mice in situ. RT-PCR studies confirmed the presence of CFTR message in freshly isolated alveolar type II (ATII) cells from wild-type mice. We patched alveolar type I (ATI) and ATII cells in freshly prepared lung slices from these mice and demonstrated the presence of 4-pS ENaC channels with the following basal open probabilities (Po): wild-type=0.21 ± 0.015: Cftr +/−=0.4 ± 0.03; ΔF508=0.55 ± 0.01; and Cftr −/−=and 0.81 ± 0.016 (means ± SE; n ≥ 9). Forskolin (5 μM) or trypsin (2 μM), applied in the pipette solution, increased the Po and number of channels in ATII cells of wild-type, Cftr +/−, and ΔF508, but not in Cftr −/− mice, suggesting that the latter were maximally activated. Western blot analysis showed that lungs of all groups of mice had similar levels of α-ENaC; however, lungs of Cftr +/− and Cftr −/− mice had significantly higher levels of an α-ENaC proteolytic fragment (65 kDa) that is associated with active ENaC channels. Our results indicate that ENaC activity is inversely correlated to predicted CFTR levels and that CFTR heterozygous and homozygous mice have higher levels of proteolytically processed ENaC fragments in their lungs. This is the first demonstration of functional ENaC-CFTR interactions in alveolar epithelial cells in situ.

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Motion-Genetic Testing is Useful in the Diagnosis of Nonhereditary Pancreatic Conditions: Arguments Against the Motion

Canadian Journal of Gastroenterology ◽

10.1155/2003/169280 ◽

2003 ◽

Vol 17 (1) ◽

pp. 53-55 ◽

Cited By ~ 9

Author(s):

Jonathan A Cohn

Keyword(s):

Cystic Fibrosis ◽

Genetic Testing ◽

Gene Interactions ◽

Transmembrane Conductance Regulator ◽

Transmembrane Conductance ◽

Cystic Fibrosis Lung Disease ◽

Increased Risk ◽

Idiopathic Chronic Pancreatitis ◽

Cystic Fibrosis Transmembrane ◽

Compound Heterozygotes

Mutations of two genes, the cystic fibrosis transmembrane conductance regulator gene (CFTR) and the pancreatic secretory trypsin inhibitor gene (PSTI), are associated with an increase in the risk of idiopathic chronic pancreatitis. Persons who have mutations of bothCFTRalleles (one severely and one mildly affected) are especially susceptible to this disease. Because these compound heterozygotes have sufficient residualCFTRfunction, they do not develop cystic fibrosis lung disease. OnePSTImutation, N34S, independently increases the risk of pancreatitis. Thus, the risk of pancreatitis is greatest among individuals who areCFTRcompound heterozygotes and who also have thePSTImutation. Nonetheless, most people withCFTRandPSTImutations do not develop pancreatitis. This fact indicates that environmental influences and gene-gene interactions also affect pancreatitis risk. AlthoughCFTRandPSTIgenetic testing can identify persons at an increased risk of pancreatitis, there are several reasons why the routine screening of individuals with nonhereditary pancreatitis is not recommended at this time: most disease-associated mutations are not detected by readily available techniques, genetic counselling guidelines do not exist, most patients with mutations do not develop pancreatitis and the results of testing do not affect the clinical management of pancreatitis.

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