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

Alejandro M. Bertorello*, Karen M. Ridge, Alexander V. Chibalin, Adrian I. Katz, Jacob I. Sznajder

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

147 Scopus citations

Abstract

Catecholamines promote lung edema clearance via β-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 β- 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 α-subunit; rather, it was the result of an increased number of α-subunits recruited from the late endosomes into the plasma membrane. The recruitment of α-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 α-subunits into the plasma membrane from an intracellular compartment in an Na+-independent manner.

Original languageEnglish (US)
Pages (from-to)L20-L27
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume276
Issue number1 20-1
DOIs
StatePublished - Jan 1999

Keywords

  • Actin cytoskeleton
  • Alveolar epithelium
  • Early endosomes
  • Late endosomes
  • Protein kinases
  • Sodium transport

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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