title: Isoproterenol increases Na+-K+-ATPase activity by membrane insertion of alpha-subunits in lung alveolar cells.
abstract: 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 microM isoproterenol for 15 min, which also resulted in a fourfold increase in the cellular levels of cAMP. Forskolin (10 microM) 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.
authors.affiliation: Department of Molecular Medicine, Karolinska Institutet, Karolinska Hospital, S-171 76 Stockholm, Sweden.
authors.forename: A M
authors.initials: AM
authors.lastname: Bertorello
authors.forename: K M
authors.initials: KM
authors.lastname: Ridge
authors.forename: A V
authors.initials: AV
authors.lastname: Chibalin
authors.forename: A I
authors.initials: AI
authors.lastname: Katz
authors.forename: J I
authors.initials: JI
authors.lastname: Sznajder
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D020126:Brefeldin A / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D011992:Endosomes / Q000201:enzymology; D007527:Isoenzymes / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D010456:Peptides, Cyclic / Q000494:pharmacology; D010766:Phosphorylation; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013997:Time Factors
chemical_list: D000318:Adrenergic beta-Agonists; D007527:Isoenzymes; D010456:Peptides, Cyclic; D005576:Colforsin; D020126:Brefeldin A; C017613:phallacidin; D000242:Cyclic AMP; D000254:Sodium-Potassium-Exchanging ATPase; D007545:Isoproterenol