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N‐acetylcysteine inhibits Na + absorption across human nasal epithelial cells
Author(s) -
Rochat Thierry,
Lacroix JeanSilvain,
Jornot Lan
Publication year - 2004
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20066
Subject(s) - epithelial sodium channel , chemistry , mucociliary clearance , amiloride , epithelial polarity , mucin , acetylcysteine , mucus , respiratory epithelium , apical membrane , intracellular , biophysics , microbiology and biotechnology , biochemistry , cell , respiratory system , medicine , biology , membrane , sodium , antioxidant , organic chemistry , lung , ecology
Abstract N‐acetylcysteine (NAC) is a widely used mucolytic drug in patients with a variety of respiratory disorders. The mechanism of action is based on rupture of the disulfide bridges of the high molecular glycoproteins present in the mucus, resulting in smaller subunits of the glycoproteins and reduced viscosity of the mucus. Because Na + absorption regulates airway surface liquid volume and thus the efficiency of mucociliary clearance, we asked whether NAC affects the bioelectric properties of human nasal epithelial cells. A 24‐h basolateral treatment with 10 mM of NAC decreased the transepithelial potential difference and short‐circuit current (I SC ) by 40%, and reduced the amiloride‐sensitive current by 50%, without affecting the transepithelial resistance. After permeabilization of the basolateral membranes of cells with amphotericin B in the presence of a mucosal‐to‐serosal Na + gradient (135:25 mM), NAC inhibited 45% of the amiloride‐sensitive current. The Na + ‐K + ‐ATPase pump activity and the basolateral K + conductance were not affected by NAC treatment. NAC did not alter total cell mRNA and protein levels of α‐epithelial Na + channel (EnaC) subunit, but reduced abundance of α‐ENaC subunits in the apical cell membrane as quantified by biotinylation. This effect can be ascribed to the sulphydryl (SH) group of NAC, since N‐acetylserine and S‐carboxymethyl‐ l ‐cysteine were ineffective. Given the importance of epithelial Na + channels in controlling the thin layer of fluid that covers the surface of the airways, the increase in the fluidity of the airway mucus following NAC treatment in vivo might be in part related to downregulation of Na + absorption and consequently water transport. J. Cell. Physiol. 201: 106–116, 2004. © 2004 Wiley‐Liss, Inc.