Effect of nitric oxide on epithelial ion transports in noncystic fibrosis and cystic fibrosis human proximal and distal airways
| Autor: | Anh Tuan Dinh-Xuan, Camille Braun, Luc Dannhoffer, Sabine Blouquit-Laye, Edouard Sage, Thierry Chinet |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Pulmonary and Respiratory Medicine
Adult Nitroprusside medicine.medical_specialty Pathology Cystic Fibrosis Purinones Physiology Bronchi Nitric Oxide Cystic fibrosis Nitric oxide Amiloride Cyclic N-Oxides chemistry.chemical_compound Young Adult Adenosine Triphosphate Fibrosis Chloride Channels Physiology (medical) Internal medicine Quinoxalines medicine Epithelial Sodium Channel Blockers Humans Nitric Oxide Donors Epithelial Sodium Channels Cyclic GMP Aged Oxadiazoles Chemistry Colforsin Imidazoles Cell Biology Free Radical Scavengers Middle Aged medicine.disease Endocrinology Guanylate Cyclase Sodium nitroprusside Airway medicine.drug |
| Zdroj: | American journal of physiology. Lung cellular and molecular physiology. 303(7) |
| ISSN: | 1522-1504 |
| Popis: | The airways of patients with cystic fibrosis (CF) exhibit decreased nitric oxide (NO) concentrations, which might affect airway function. The aim of this study was to determine the effects of NO on ion transport in human airway epithelia. Primary cultures of non-CF and CF bronchial and bronchiolar epithelial cells were exposed to the NO donor sodium nitroprusside (SNP), and bioelectric variables were measured in Ussing chambers. Amiloride was added to inhibit the Na+channel ENaC, and forskolin and ATP were added successively to stimulate cAMP- and Ca2+-dependent Cl−secretions, respectively. The involvement of cGMP was assessed by measuring the intracellular cGMP concentration in bronchial cells exposed to SNP and the ion transports in cultures exposed to 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one, an inhibitor of the soluble guanylate cyclase (ODQ), or to 8Z, a cocktail of 8-bromo-cGMP and zaprinast (phosphodiesterase 5 inhibitor). SNP decreased the baseline short-circuit current ( Isc) and the changes in Iscinduced by amiloride, forskolin, and ATP in non-CF bronchial and bronchiolar cultures. The mechanism of this inhibition was studied in bronchial cells. SNP increased the intracellular cGMP concentration ([cGMP]i). The inhibitory effect of SNP was abolished by 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, an NO scavenger (PTIO) and ODQ and was partly mimicked by increasing [cGMP]i. In CF cultures, SNP did not significantly modify ion transport; in CF bronchial cells, 8Z had no effect; however, SNP increased the [cGMP]i. In conclusion, exogenous NO may reduce transepithelial Na+absorption and Cl−secretion in human non-CF airway epithelia through a cGMP-dependent pathway. In CF airways, the NO/cGMP pathway appears to exert no effect on transepithelial ion transport. |
| Databáze: | OpenAIRE |
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