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Am J Physiol Lung Cell Mol Physiol 276: L20-L27, 1999;
1040-0605/99 $5.00
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Vol. 276, Issue 1, L20-L27, January 1999

Isoproterenol increases Na+-K+-ATPase activity by membrane insertion of alpha -subunits in lung alveolar cells

Alejandro M. Bertorello1, Karen M. Ridge2, Alexander V. Chibalin1, Adrian I. Katz3, and Jacob I. Sznajder2

1 Department of Molecular Medicine, Karolinska Institutet, Karolinska Hospital, S-171 76 Stockholm, Sweden; 2 Department of Pulmonary and Critical Care Medicine, Michael Reese Hospital, University of Illinois at Chicago, Chicago 60616; and 3 Department of Medicine, University of Chicago, Chicago, Illinois 60637

Catecholamines promote lung edema clearance via beta -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 beta -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 alpha -subunit; rather, it was the result of an increased number of alpha -subunits recruited from the late endosomes into the plasma membrane. The recruitment of alpha -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 alpha -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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