title: Effect of nitric oxide on epithelial ion transports in noncystic fibrosis and cystic fibrosis human proximal and distal airways.
abstract: 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 Ca(2+)-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 (I(sc)) and the changes in I(sc) induced 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.
authors: UPRES EA220, UFR Paris Ile de France Ouest, Université de Versailles Saint Quentin en Yvelines, Boulogne, France. sabine.blouquit-laye@uvsq.fr
authors: Sabine
authors: S
authors: Blouquit-Laye
authors: Luc
authors: L
authors: Dannhoffer
authors: Camille
authors: C
authors: Braun
authors: Anh-Tuan
authors: AT
authors: Dinh-Xuan
authors: Edouard
authors: E
authors: Sage
authors: Thierry
authors: T
authors: Chinet
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000584:Amiloride / Q000494:pharmacology; D001980:Bronchi / Q000187:drug effects*; D018118:Chloride Channels / Q000187:drug effects*; D005576:Colforsin / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000032:analysis / Q000494:pharmacology; D003497:Cyclic N-Oxides / Q000494:pharmacology; D003550:Cystic Fibrosis / Q000188:drug therapy*; D062686:Epithelial Sodium Channel Blockers / Q000494:pharmacology; D053503:Epithelial Sodium Channels / Q000187:drug effects*; D016166:Free Radical Scavengers / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008875:Middle Aged; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D011688:Purinones / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D055815:Young Adult
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D018118:Chloride Channels; D003497:Cyclic N-Oxides; D062686:Epithelial Sodium Channel Blockers; D053503:Epithelial Sodium Channels; D016166:Free Radical Scavengers; D007093:Imidazoles; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D011688:Purinones; D011810:Quinoxalines; D009599:Nitroprusside; C079391:2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide; D005576:Colforsin; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D000584:Amiloride; D000255:Adenosine Triphosphate; D006162:Guanylate Cyclase; C011145:zaprinast; D006152:Cyclic GMP