Molecular and cellular biology of cystic fibrosis

McPherson, Margaret A.; Dormer, Robert L.

doi:10.1016/0098-2997(91)90015-e

Cited by 19 publications

(7 citation statements)

References 248 publications

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“…McPherson et al demonstrated an alteration of [3-adrenergic stimulation of mucin secretion by CF submandibular cells while [3-agonists were able to generate intracellular cyclic AMP in the same manner in normal and CF cells [29]. The authors postulated an alteration in a regulatory mechanism distal to the second messenger system.…”

Section: Discussionmentioning

confidence: 99%

“…Forskolin, which raised intracellular cAMP, stimulated C1-secretion by increasing the magnitude of CFTR-mediated C1 conductance in the apical membrane [32], by a PKAdependent stimulus, was capable of stimulating mucin secretion in a Ca2+-independent manner [33]. In addition, the above mentioned results of McPherson and Dormer [29] who have shown a defect in [3-adrenergic stimulation of mucin and serous protein secretion from submandibular salivary tissues from CF patients and those of Bradbury et al [34] demonstrating the correction by transfection of wild type CFTR, of the defect in cAMP-mediated endocytosis and exocytosis in CFPAC-1 cells also correlated closely with our findings.…”

Section: Discussionmentioning

confidence: 99%

“…The lack of responsiveness to ATP by the CF cells is unlikely to derive from an absence of the receptor on the pathological cells or from an alteration in transduction mechanisms since normal and CF cells respond similarly to ATP by transient intracellular calcium mobilization. McPherson et al demonstrated an alteration of [3-adrenergic stimulation of mucin secretion by CF submandibular cells while [3-agonists were able to generate intracellular cyclic AMP in the same manner in normal and CF cells [29]. The authors postulated an alteration in a regulatory mechanism distal to the second messenger system.…”

Section: Discussionmentioning

confidence: 99%

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Defective ATP‐dependent mucin secretion by cystic fibrosis pancreatic epithelial cells

1996

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Defective ATP‐dependent mucin secretion by cystic fibrosis pancreatic epithelial cells

1996

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“…In cystic fibrosis (CF), alterations in cystic fibrosis transmembrane conductance regulator (CFTR) protein lead to an impermeability of the luminal surface to chloride (1)(2)(3). The resulting chloride-defective secretions, coupled with an excessive absorption of sodium (4), are responsible for the reduction in fluid secretion across the CF respiratory epithelium (5), contributing to substantial dehydration and alterations of osmolarity of the periciliary and gel layers.…”

mentioning

confidence: 99%

Revisited Physicochemical and Transport Properties of Respiratory Mucus in Genotyped Cystic Fibrosis Patients

Deneuville

Perrot-Minot

Pennaforte

et al. 1997

Am J Respir Crit Care Med

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We investigated the physicochemical and transport properties of sputum samples collected in physiotherapy from a well-documented group of 27 cystic fibrosis (CF) patients with identified CF genotypes. Sputum samples were characterized ex vivo for their water content, surface properties (surface tension and contact angle), rheologic properties (viscosity and elastic modulus), and transport properties (mucociliary and cough transport). These data were analyzed in relation to the clinical status of the patients (FEV1, FVC, Shwachman score, Brasfield score, nutritional status), their genotype, and the degree of infection of their sputa (leukocyte and Pseudomonas aeruginosa counts). We observed negative and significant correlations between mucociliary transport and elastic modulus of the patients' sputum (r = -0.63, p < 0.01), and between the cough transport and contact angle of the sputum (r = -0.81, p < 0.0001), respectively. The P. aeruginosa count was also significantly correlated with the sputum water content (r = -0.53, p < 0.02) as well as with the cough transport of the sputum (r = -0.62, p < 0.01). In CF patients with a sputum leukocyte count > 2,000/mm3, the sputum water content (p < 0.02), FEV1 (p < 0.05) and FVC (p < 0.02) were significantly lower than those of CF patients with a leukocyte count < or = 2,000/mm3. CF patients with a homozygous delta F 508 genotype had significantly greater values of sputum water content (p < 0.05), and cough-transport capacity (p < 0.05) than did heterozygous patients. No correlation was observed between the sputum properties and any of the clinical data. These results suggest that the control of infection should be emphasized in CF, since it can directly or indirectly modulate the degree of hydration, and therefore the physicochemical and transport properties, of airway secretions.

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“…Cystic ¢brosis (CF) is an autosomal recessive disease characterised by disturbances in ion transport and viscous epithelial mucous secretions [1,2]. The cystic ¢brosis gene protein, the cystic ¢brosis transmembrane conductance regulator protein (CFTR), acts as a Cl 3 channel [3] and we have shown it to be a key regulator of protein secretion [4^8].…”

Section: Introductionmentioning

confidence: 99%

A cyclic nucleotide PDE5 inhibitor corrects defective mucin secretion in submandibular cells containing antibody directed against the cystic fibrosis transmembrane conductance regulator protein

et al. 1999

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A selective cyclic nucleotide PDE5 inhibitor corrected the defective mucin secretion response to the L L-agonist isoproterenol in submandibular acinar cells inhibited by antibody directed against the cystic fibrosis transmembrane conductance regulator. The PDE5 inhibitor was as effective as cpt-cyclic AMP or a selective PDE4 inhibitor. However, the PDE5 inhibitor had no effect on basal or isoproterenol-stimulated cyclic AMP levels and did not stimulate mucin secretion. The results showing, for the first time, correction of the CFTR mucin secretion defect by a PDE5 inhibitor, which may involve cyclic GMP, will have a major impact in development of a rational drug treatment for cystic fibrosis.z 1999 Federation of European Biochemical Societies.

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Molecular and cellular biology of cystic fibrosis

Cited by 19 publications

References 248 publications

Defective ATP‐dependent mucin secretion by cystic fibrosis pancreatic epithelial cells

Defective ATP‐dependent mucin secretion by cystic fibrosis pancreatic epithelial cells

Revisited Physicochemical and Transport Properties of Respiratory Mucus in Genotyped Cystic Fibrosis Patients

A cyclic nucleotide PDE5 inhibitor corrects defective mucin secretion in submandibular cells containing antibody directed against the cystic fibrosis transmembrane conductance regulator protein

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