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Augmentation of Endogenous Dopamine Production Increases Lung Liquid Clearance

Department of Medicine, Northwestern University, Feinberg School of Medicine, Chicago, Illinois; Technion, Israel Institute of Technology, Haifa, Israel; Department of Medicine, Atherosclerosis Research Unit, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden; and Pulmonary, Allergy, and Critical Care Medicine, Columbia University College of Physicians and Surgeons, New York, New York

Correspondence and requests for reprints should be addressed to Jacob I. Sznajder, M.D., Pulmonary and Critical Care Medicine, Northwestern University, 303 East Chicago, Tarry 14-707, Chicago, IL 60611-3010. 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 dopamine 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 (AADC) and, when incubated with the dopamine precursor, 3-hydroxy-L-tyrosine (L-dopa), produce dopamine. Rats fed TSD, a precursor of L-dopa and dopamine, had increased urinary dopamine levels, which were inhibited by benserazide, an inhibitor of AADC. Rats fed TSD for 15, 24, and 48 hours had a 26, 46, and 45% increase in lung liquid clearance, respectively, as compared with controls. Also, dopaminergic D₁ receptor antagonist—but not dopaminergic D₂ receptor antagonist—inhibited the TSD-mediated increase in lung liquid clearance. Alveolar Type II cells isolated from the lungs of rats after they had been fed TSD for 24 hours demonstrated increased protein abundance of Na,K-ATPase ₁ and ß₁ subunits. Basolateral membranes isolated from peripheral lung tissue of tyrosine-fed rats had increased Na,K-ATPase activity and Na,K-ATPase ₁ subunit. These data provide the first evidence that alveolar epithelial cells produce dopamine and that increasing endogenous dopamine increases lung liquid clearance.

Key Words: dopamine • lung epithelium • Na,K-ATPase • tyrosine diet

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