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Published ahead of print on December 30, 2003, doi:10.1164/rccm.200207-744OC

Am. J. Respir. Crit. Care Med., Volume 169, Number 6, March 2004, 757-763

A more recent version of this article appeared on March 15, 2004
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Submitted on July 24, 2002
Accepted on December 23, 2003

Augmentation of Endogenous Dopamine Production Increases Lung Liquid Clearance

Yochai Adir1, Zaher S Azzam, Emilia Lecuona1, Sergio Leal1, Liuska Pesce1, Vidas Dumasius1, Alejandro M Bertorello, Phillip Factor1, James B Young1, Karen M Ridge1, and Jacob Iasha Sznajder1*

1 Medicine, Northwestern University, Chicago, IL, USA

* To whom correspondence should be addressed. E-mail: j-sznajder{at}northwestern.edu.

We have previously reported that dopamine increased active Na+ transport in rat lungs by upregulating the alveolar epithelial Na,K-ATPase. Here we tested whether alveolar epithelial cells produce dopamine and whether increasing endogenous DA production by feeding rats a 4% tyrosine diet (TSD) would increase lung liquid clearance. Alveolar type II cells express the enzyme aromatic L-amino acid decarboxylase and when incubated with the dopamine precursor, L-DOPA, produce dopamine. Rats fed with TSD, a precursor of L-DOPA and dopamine, had increased urinary dopamine levels, which were inhibited by benserazide, an inhibitor of L-amino acid dopa decarboxylase. Rats fed with TSD for 15, 24 and 48 hours had 26%, 46% and 45% increase in lung liquid clearance, respectively, as compared to controls. Also, dopaminergic D1 receptor antagonist but not dopaminergic D2 receptor antagonist- inhibited the TSD mediated increase in lung liquid clearance. ATII cells isolated from rat's lungs after 24 hours of TSD demonstrated increased protein abundance of {alpha}1 and {beta}1 Na,K-ATPase. Basolateral membranes isolated from peripheral lung tissue of tyrosine fed rats had increased Na,K-ATPase activity and {alpha}1 Na,K-ATPase subunit. These data provide the first evidence that alveolar epithelial cells produce dopamine and that increasing endogenous dopamine increases lung liquid clearance.


Key words: Active Na+ transport, lung epithelium, tyrosine, dopamine, Na,K-ATPase




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