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-subunits in lung alveolar
cells
1 Department of Molecular
Medicine, Karolinska Institutet, Karolinska Hospital, S-171 76 Stockholm, Sweden; 2 Department of
Pulmonary and Critical Care Medicine,
Catecholamines promote lung edema clearance via
-adrenergic-mediated stimulation of active
Na+ transport across the alveolar
epithelium. Because alveolar epithelial type II cell
Na+-K+-ATPase
contributes to vectorial Na+ flux,
the present study was designed to investigate whether
Na+-K+-ATPase
undergoes acute changes in its catalytic activity in response to
-adrenergic-receptor stimulation.
Na+-K+-ATPase
activity increased threefold in cells incubated with 1 µM
isoproterenol for 15 min, which also resulted in a fourfold increase in
the cellular levels of cAMP. Forskolin (10 µM) also stimulated
Na+-K+-ATPase
activity as well as ouabain binding. The increase in
Na+-K+-ATPase
activity was abolished when cells were coincubated with a
cAMP-dependent protein kinase inhibitor. This stimulation, however, was
not due to protein kinase-dependent phosphorylation of the Na+-K+-ATPase
-subunit; rather, it was the result of an increased number of
-subunits recruited from the late endosomes into the plasma membrane. The recruitment of
-subunits to the plasma membrane was
prevented by stabilizing the cortical actin cytoskeleton with phallacidin or by blocking anterograde transport with brefeldin A but
was unaffected by coincubation with amiloride. In conclusion, isoproterenol increases
Na+-K+-ATPase
activity in alveolar type II epithelial cells by recruiting
-subunits into the plasma membrane from an intracellular compartment in an Na+-independent manner.
alveolar epithelium; protein kinases; actin cytoskeleton; sodium transport; early endosomes; late endosomes
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