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

Free Radic Biol Med 2010 Jul 24;49(2):294-300. Epub 2010 Apr 24.

Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.freeradbiomed.2010.04.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2916064PMC
July 2010
2 Reads

Publication Analysis

Top Keywords

alveolar epithelium
12
gas
9
inhaled gas
8
extracellular s-nitroso-l-cysteine
8
l-cysteine uptake
8
gas enters
8
alveolar
5
d-cysteine+/-lat competitors
4
competitors gas
4
gas exposure
4
conclude gas
4
lat dependence
4
intracellular s-nitrosothiol
4
s-nitrosothiol levels
4
increased intracellular
4
dependently increased
4
concentration dependently
4
dependence conclude
4
exposure concentration
4
gas uptake
4

Similar Publications