Na+ transport in cystic fibrosis respiratory epithelia. Abnormal basal rate and response to adenylate cyclase activation.
TLDR
It is concluded that CF airway epithelia absorb Na+ at an accelerated rate due to an abnormal CF beta receptor because similar effects were induced by forskolin, and because cAMP production was similar in normal and CF epithelium.Abstract:
The transepithelial potential difference (PD) of cystic fibrosis (CF) airway epithelium is abnormally raised and the Cl- permeability is low. We studied the contribution of active Na+ absorption to the PD and attempted to increase the Cl- permeability of CF epithelia. Nasal epithelia from CF and control subjects were mounted in Ussing chambers and were short-circuited. The basal rate of Na+ absorption was raised in CF polyps compared with control tissues. Whereas beta agonists induced Cl- secretion in normal and atopic epithelia, beta agonists further increased the rate of Na+ absorption in CF epithelia without inducing Cl- secretion. This unusual effect is not due to an abnormal CF beta receptor because similar effects were induced by forskolin, and because cAMP production was similar in normal and CF epithelia. We conclude that CF airway epithelia absorb Na+ at an accelerated rate. The abnormal response to beta agonists may reflect a primary abnormality in a cAMP-modulated path, or a normal cAMP-modulated process in a Cl- impermeable epithelial cell.read more
Citations
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Lung Infections Associated with Cystic Fibrosis
Jeffrey B. Lyczak,Carolyn L. Cannon,Carolyn L. Cannon,Carolyn L. Cannon,Gerald B. Pier,Gerald B. Pier +5 more
TL;DR: As the modalities of CF research have changed over the decades from empirical histological studies to include biophysical measurements of CFTR function, the clinical management of this disease has similarly evolved to effectively address the ever-changing spectrum of CF-related infectious diseases.
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Molecular Structure and Physiological Function of Chloride Channels
TL;DR: The loss of distinct Cl- channels leads to an impairment of transepithelial transport in cystic fibrosis and Bartter's syndrome, to increased muscle excitability in myotonia congenita, to reduced endosomal acidification and impaired endocytosis in Dent's disease, and to impaired extracellular acidification by osteoclasts and osteopetrosis.
Journal ArticleDOI
Effects of reduced mucus oxygen concentration in airway Pseudomonas infections of cystic fibrosis patients
D. Worlitzsch,Robert Tarran,Martina Ulrich,Ute E. Schwab,Aynur Cekici,Keith C. Meyer,Peter Birrer,Gabriel Bellon,Jürgen Berger,Tilo Weiss,Konrad Botzenhart,James R. Yankaskas,Scott H. Randell,Richard C. Boucher,Gerd Döring +14 more
TL;DR: In CF patients with established lung disease, Pseudomonas aeruginosa was located within hypoxic mucopurulent masses in airway lumens, and in vitro studies revealed that CF-specific increases in epithelial O(2) consumption, linked to increased airway surface liquid (ASL) volume absorption and mucus stasis, generated steep hypoxic gradients within thickened mucus on CF epithelial surfaces prior to infection.
Journal ArticleDOI
CFTR as a cAMP-dependent regulator of sodium channels.
M. J. Stutts,Cecilia M. Canessa,John C. Olsen,M Hamrick,Jonathan A. Cohn,Bernard C. Rossier,Richard C. Boucher +6 more
TL;DR: In CF airway epithelia, the absence of this second function of CFTR as a cAMP-dependent regulator likely accounts for abnormal sodium transport.
Journal ArticleDOI
Structure and Function of the CFTR Chloride Channel
TL;DR: Current knowledge of CFTR structure and function may help better its mechanism of action, its role in electrolyte transport, its dysfunction in cystic fibrosis, and its relationship to other ABC transporters.
References
More filters
Journal ArticleDOI
A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding
TL;DR: This assay is very reproducible and rapid with the dye binding process virtually complete in approximately 2 min with good color stability for 1 hr with little or no interference from cations such as sodium or potassium nor from carbohydrates such as sucrose.
Journal ArticleDOI
Active transport of sodium as the source of electric current in the short-circuited isolated frog skin.
Hans H. Ussing,K. Zerahn +1 more
Journal ArticleDOI
Radioimmunoassay for Cyclic Nucleotides I. PREPARATION OF ANTIBODIES AND IODINATED CYCLIC NUCLEOTIDES
TL;DR: Sensitive and reproducible radioimmunoassays have been developed for cyclic adenosine 3',5'-monophosphate (cAMP), cyclic guanosine 3,5'- monophosphates (cGMP), cycled inosine 3,'5'-MonophosphATE (cIMP), and cyclic uridine 3',4'-monophile (cUMP) based upon competition of the cyclic nucleotide with isotopically labeled cyclic
Journal ArticleDOI
Forskolin: unique diterpene activator of adenylate cyclase in membranes and in intact cells.
TL;DR: F Forskolin would appear to activate adenylate cyclase through a unique mechanism involving both direct activation of the enzyme and facilitation or potentiation of the modulation of enzyme activity by receptors or the guanyl nucleotide-binding subunit, or both.
Journal ArticleDOI
Chloride impermeability in cystic fibrosis.
Paul M. Quinton,Paul M. Quinton +1 more
TL;DR: Results are reported which suggest that abnormally low Cl− permeability in cystic fibrosis leads to poor reabsorption of NaCl in the sweat duct, and hence to a high concentration of Na Cl in theSweat duct.