title: Nitric oxide has no beneficial effects on ion transport defects in cystic fibrosis human nasal epithelium.
abstract: Nitric oxide (NO) has been reported to activate Cl- secretion via the cystic fibrosis transmembrane conductance regulator (CFTR) and inhibit epithelial Na+ absorption mediated by amiloride-sensitive epithelial Na+ channels (ENaC). These ion transport systems are defective in cystic fibrosis (CF): Cl- secretion by CFTR is impaired and Na+ absorption by ENaC is dramatically increased. By activating CFTR and depressing ENaC, NO is a potentially beneficial therapeutic agent for ion transport defects in human CF respiratory epithelia. To assess the effects of NO on human respiratory epithelial cells, the NO donors sodium nitroprusside (SNP) and spermine NONOate were applied to primary cultured nasal cells, surgically obtained from non-CF and CF patients. Measurements of transepithelial short-circuit current (ISC) showed that NO has no inhibitory potency against amiloride-sensitive nasal ENaC (nENaC) or amiloride-insensitive Na+-absorbing mechanisms in non-CF and CF epithelia. Furthermore, NO had no stimulatory effect on Cl- secretion by CFTR or any other Cl- conductance pathway in either tissue. Although NO elevated the intracellular Ca2+ concentration, we did not detect any activation of Ca2+-dependent Cl- channels. These results demonstrate that NO has no beneficial effect on CF epithelial cells of the upper airways.
authors.affiliation: CF Working Group Giessen, Justus-Liebig-University, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Rückes-Nilges
authors.forename: H
authors.initials: H
authors.lastname: Lindemann
authors.forename: T
authors.initials: T
authors.lastname: Klimek
authors.forename: H
authors.initials: H
authors.lastname: Glanz
authors.forename: W M
authors.initials: WM
authors.lastname: Weber
mesh_terms: D000042:Absorption; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D018118:Chloride Channels / Q000502:physiology; D002712:Chlorides / Q000378:metabolism; D003550:Cystic Fibrosis / Q000378:metabolism*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000502:physiology; D004553:Electric Conductivity; D006801:Humans; D007473:Ion Channels / Q000187:drug effects* / Q000502:physiology*; D009297:Nasal Mucosa / Q000378:metabolism*; D009569:Nitric Oxide / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009589:Nitrogen Oxides; D009599:Nitroprusside / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D013096:Spermine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C505032:CFTR protein, human; D018118:Chloride Channels; D002712:Chlorides; D007473:Ion Channels; D020030:Nitric Oxide Donors; D009589:Nitrogen Oxides; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; C091861:spermine nitric oxide complex; D009599:Nitroprusside; D013096:Spermine; D009569:Nitric Oxide; D012964:Sodium; D002118:Calcium