Dopamine regulates Na-K-ATPase in alveolar epithelial cells via MAPK-ERK-dependent mechanisms

Carmen Guerrero, Emilia Lecuona, Liuska Pesce, Karen M. Ridge, Jacob I. Sznajder*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

Dopamine (DA) increases lung edema clearance by regulating vectorial Na+ transport and Na-K-ATPase in the pulmonary epithelium. We studied the role of the mitogen-activated protein kinase (MAPK)-extracellular signal-regulated kinase (ERK) pathway in the DA regulation of Na-K-ATPase in alveolar epithelial cells (AEC). Incubation of AEC with DA resulted in a rapid stimulation of ERK activity via dopaminergic type 2 receptors. Analysis of total RNA and protein showed a 1.5-fold increase in the Na-K-ATPase β1-subunit mRNA levels and up to a fivefold increase in β1-subunit protein abundance after DA stimulation, which was blocked by the MAPK kinase (MEK) inhibitors PD-98059 and U-0126. Also, the DA-ERK pathway stimulated the synthesis of a green fluorescent protein reporter gene driven by the β1-subunit promoter, which indicates that DA regulates the Na-K-ATPase β1-subunit at the transcriptional level. The DA-mediated increase in β1-subunit mRNA protein resulted in an increase in functional Na pumps in the basolateral membranes of alveolar type II cells. These results suggest that the MAPK-ERK pathway is an important mechanism in the regulation of Na-K-ATPase by DA in the alveolar epithelium.

Original languageEnglish (US)
Pages (from-to)L79-L85
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume281
Issue number1 25-1
DOIs
StatePublished - 2001

Keywords

  • Alveolar type II cells
  • Basolateral membrane
  • Green fluorescent protein
  • Transcriptional regulation

ASJC Scopus subject areas

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

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