Enhancement of airway epithelial na-,k--atpase activity by nitrogen
dioxide and the protective role of nordihydroguaiaretic acid.
Robison, Timothy W., and Kwang-Jin Kim.
DEPARTMENTS OF MOLECULAR PHARMACOLOGY AND TOXICOLOGY, PEDIATRICS
MEDICINE, PHYSIOLOGY AND BIOPHYSICS, BIOMEDICAL ENGINEERING, AND WILL
ROGERS INSTITUTE PULMONARY RESEARCH CENTER, UNIVERSITY OF SOUTHERN
CALIFORNIA, LOS ANGELES, CA
APStracts 2:0183L, 1995.
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 hr
exposure of GPTE monolayers to 5 ppm NO2 increased ouabain-sensitive
86Rb uptake (nmoles/mg protein/30 min) 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 pmoles/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 [mu]M, respectively, in
comparison with an air control of 0.53 +/- 0.02 [mu]M. 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
(NDGA), an antioxidant, blocked the increase of ouabain-sensitive
86Rb uptake almost completely and partially protected transepithelial
resistance suggesting that lipid peroxidation processes may play a
role in alterations of airway epithelial barrier and active ion
transport properties.
Received 9 May 1995; accepted in final form 8 September 1995.
APS Manuscript Number L142-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 6 November 95