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Vol. 13, Issue 4, 1381-1389, April 2002
and -
*Pulmonary and Critical Care Medicine, Northwestern University
Medical School, Chicago, Illinois 60611; The purpose of this study was to define mechanisms by which
dopamine (DA) regulates the Na,K-ATPase in alveolar epithelial type 2 (AT2) cells. The Na,K-ATPase activity increased by twofold in cells
incubated with either 1 µM DA or a dopaminergic D1
agonist, fenoldopam, but not with the dopaminergic D2
agonist quinpirole. The increase in activity paralleled an increase in
Na,K-ATPase Department of
Molecular Medicine, Karolinska Institutet, Karolinska Hospital, S-171
76 Stockholm, Sweden; §Department of Molecular
Pharmacology, Stanford University School of Medicine, Stanford,
California 94305, and Department of Medicine, University
of Chicago, Chicago, Illinois 60637
1 and 
1 protein abundance in the basolateral membrane
(BLM) of AT2 cells. This increase in protein abundance was mediated by
the exocytosis of Na,K-pumps from late endosomal compartments into the
BLM. Down-regulation of diacylglycerol-sensitive types of protein
kinase C (PKC) by pretreatment with phorbol 12-myristate 13-acetate or inhibition with bisindolylmaleimide prevented the DA-mediated increase in Na,K-ATPase activity and exocytosis of Na,K-pumps to the BLM. Preincubation of AT2 cells with either 2-[1-(3-dimethylaminopropyl)-5-methoxyindol-3-yl]-3-(1H-indol-3-yl)maleimide (Gö6983), a selective inhibitor of PKC-
, or
isozyme-specific inhibitor peptides for PKC- or PKC-
inhibited
the DA-mediated increase in Na,K-ATPase. PKC- and PKC-, but not
PKC- or -, translocated from the cytosol to the membrane fraction
after exposure to DA. PKC-- and PKC--specific peptide agonists
increased Na,K-ATPase protein abundance in the BLM. Accordingly,
dopamine increased Na,K-ATPase activity in alveolar epithelial cells
through the exocytosis of Na,K-pumps from late endosomes into the
basolateral membrane in a mechanism-dependent activation of the novel
protein kinase C isozymes PKC- and PKC-.
Corresponding author. E-mail
address: sznajder{at}northwestern.edu.
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