Enhancement of airway epithelial Na+,K(+)-ATPase activity by NO2 and protective role of nordihydroguaiaretic acid.
We examined the effects of nitrogen dioxide (NO2) on guinea pig tracheobronchial (GPTE) ouabain-sensitive 86Rb uptake, as an index of Na+,K(+)-ATPase activity, and specific [3H]ouabain binding. A 1-h exposure of GPTE monolayers to 5 ppm NO2 increased ouabain-sensitive 86Rb uptake (nmol.mg protein-1.30 min-1) to 512 +/- 39 compared with an air-control value of 278 +/- 20. Similarly, 1 ppm NO2 increased 86Rb uptake to 336 +/- 19 from an air control of 219 +/- 31. The specific [3H]ouabain-binding capacity (Bmax) for monolayers exposed to 5 ppm NO2 was increased to 23.2 +/- 1.2 pmol/mg protein in comparison with an air-control value of 18.4 +/- 0.4; however, there was no change at 1 ppm NO2. Binding constants (Kd) for 1 or 5 ppm NO2 were increased to 0.64 +/- 0.02 and 0.79 +/- 0.08 microM, respectively, in comparison with an air-control value of 0.53 +/- 0.02 microM. Changes of Bmax and Kd may be consistent with a recruitment of latent pumps to the basolateral cell plasma membrane and/or increased turnover of the sodium pump. However, the increase of Bmax was no more than 126% of the air control, while 86Rb uptake increased to 184%, suggesting that an increased turnover is the more predominant effect. Incubation of GPTE monolayers during NO2 exposure with nordihydroguaiaretic acid, an antioxidant, blocked the increase of ouabain-sensitive 86Rb uptake almost completely and partially protected transepithetial resistance, suggesting that lipid peroxidation processes may play a role in alterations of airway epithelial barrier and active ion transport properties.
Robison
T W
TW
Department of Molecular Pharmacology and Toxicology, University of Southern California, Los Angeles 90033, USA.
Kim
K J
KJ
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004594:Electrophysiology; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D008297:Male; D009637:Masoprocol / Q000494:pharmacology*; D009585:Nitrogen Dioxide / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D014132:Trachea / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D000975:Antioxidants; D009637:Masoprocol; D000254:Sodium-Potassium-Exchanging ATPase; D009585:Nitrogen Dioxide