Transport rather than diffusion-dependent route for nitric oxide gas activity in alveolar epithelium.

Journal Article (Journal Article)

The pathway by which inhaled NO gas enters pulmonary alveolar epithelial cells has not been directly tested. Although the expected mechanism is diffusion, another route is the formation of S-nitroso-L-cysteine, which then enters the cell through the L-type amino acid transporter (LAT). To determine if NO gas also enters alveolar epithelium this way, we exposed alveolar epithelial-rat type I, type II, L2, R3/1, and human A549-cells to NO gas at the air liquid interface in the presence of L- and D-cysteine+/-LAT competitors. NO gas exposure concentration dependently increased intracellular NO and S-nitrosothiol levels in the presence of L- but not D-cysteine, which was inhibited by LAT competitors, and was inversely proportional to diffusion distance. The effect of L-cysteine on NO uptake was also concentration dependent. Without preincubation with L-cysteine, NO uptake was significantly reduced. We found similar effects using ethyl nitrite gas in place of NO. Exposure to either gas induced activation of soluble guanylyl cylase in a parallel manner, consistent with LAT dependence. We conclude that NO gas uptake by alveolar epithelium achieves NO-based signaling predominantly by forming extracellular S-nitroso-L-cysteine that is taken up through LAT, rather than by diffusion. Augmenting extracellular S-nitroso-L-cysteine formation may augment pharmacological actions of inhaled NO gas.

Full Text

Duke Authors

Cited Authors

  • Brahmajothi, MV; Mason, SN; Whorton, AR; McMahon, TJ; Auten, RL

Published Date

  • July 15, 2010

Published In

Volume / Issue

  • 49 / 2

Start / End Page

  • 294 - 300

PubMed ID

  • 20423728

Pubmed Central ID

  • PMC2916064

Electronic International Standard Serial Number (EISSN)

  • 1873-4596

Digital Object Identifier (DOI)

  • 10.1016/j.freeradbiomed.2010.04.020


  • eng

Conference Location

  • United States