Linked Life Data

14701827

Source:http://linkedlifedata.com/resource/pubmed/id/14701827

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2004-3-8
pubmed:abstractText
Cystic fibrosis (CF) is caused by defective cyclic AMP-dependent cystic fibrosis transmembrane conductance regulator Cl(-) channels. Thus, CF epithelia fail to transport Cl(-) and water. A postulated therapeutic avenue in CF is activation of alternative Ca(2+)-dependent Cl(-) channels. We hypothesized that stimulation of Ca(2+) entry from the extracellular space could trigger a sustained Ca(2+) signal to activate Ca(2+)-dependent Cl(-) channels. Cytosolic [Ca(2+)](i) was measured in non-polarized human CF (IB3-1) and non-CF (16HBE14o(-)) airway epithelial cells. Primary human CF and non-CF airway epithelial monolayers as well as Calu-3 monolayers were used to assess anion secretion. In vivo nasal potential difference measurements were performed in non-CF and two different CF mouse (DeltaF508 homozygous and bitransgenic gut-corrected but lung-null) models. Zinc and ATP induced a sustained, reversible, and reproducible increase in cytosolic Ca(2+) in CF and non-CF cells with chemistry and pharmacology most consistent with activation of P2X purinergic receptor channels. P2X purinergic receptor channel-mediated Ca(2+) entry stimulated sustained Cl(-) and HCO(3)(-) secretion in CF and non-CF epithelial monolayers. In non-CF mice, zinc and ATP induced a significant Cl(-) secretory response similar to the effects of agonists that increase intracellular cAMP levels. More importantly, in both CF mouse models, Cl(-) permeability of nasal epithelia was restored in a sustained manner by zinc and ATP. These effects were reversible and reacquirable upon removal and readdition of agonists. Our data suggest that activation of P2X calcium entry channels may have profound therapeutic benefit for CF that is independent of cystic fibrosis transmembrane conductance regulator genotype.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10720-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:14701827-Adenosine Triphosphate, pubmed-meshheading:14701827-Animals, pubmed-meshheading:14701827-Anions, pubmed-meshheading:14701827-Calcium, pubmed-meshheading:14701827-Cell Line, pubmed-meshheading:14701827-Cells, Cultured, pubmed-meshheading:14701827-Chlorides, pubmed-meshheading:14701827-Chlorine, pubmed-meshheading:14701827-Coloring Agents, pubmed-meshheading:14701827-Cyclic AMP, pubmed-meshheading:14701827-Cystic Fibrosis, pubmed-meshheading:14701827-Cystic Fibrosis Transmembrane Conductance Regulator, pubmed-meshheading:14701827-Cytosol, pubmed-meshheading:14701827-Epithelial Cells, pubmed-meshheading:14701827-Fura-2, pubmed-meshheading:14701827-Genotype, pubmed-meshheading:14701827-Homozygote, pubmed-meshheading:14701827-Humans, pubmed-meshheading:14701827-Hydrogen-Ion Concentration, pubmed-meshheading:14701827-Mice, pubmed-meshheading:14701827-Mutation, pubmed-meshheading:14701827-Receptors, Purinergic P2, pubmed-meshheading:14701827-Time Factors, pubmed-meshheading:14701827-Trachea, pubmed-meshheading:14701827-Zinc
pubmed:year
2004
pubmed:articleTitle
Extracellular zinc and ATP restore chloride secretion across cystic fibrosis airway epithelia by triggering calcium entry.
pubmed:affiliation
Department of Physiology and Biophysics, Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama, Birmingham 35294-0005, USA. zsembery@physiology.uab.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't