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
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 1 and 1 Na,K-ATPase. Basolateral membranes isolated from peripheral lung tissue of tyrosine fed rats had increased Na,K-ATPase activity and 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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