Dopamine regulates Na-K-ATPase in alveolar epithelial cells via MAPK-ERK-dependent mechanisms.
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 beta1-subunit mRNA levels and up to a fivefold increase in beta1-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 beta1-subunit promoter, which indicates that DA regulates the Na-K-ATPase beta1-subunit at the transcriptional level. The DA-mediated increase in beta1-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.
Guerrero
C
C
Division of Pulmonary and Critical Care Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Lecuona
E
E
Pesce
L
L
Ridge
K M
KM
Sznajder
J I
JI
D000818:Animals; D002478:Cells, Cultured; D004298:Dopamine / Q000494:pharmacology / Q000502:physiology*; D004789:Enzyme Activation; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology; D007425:Intracellular Membranes / Q000378:metabolism; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology
D007527:Isoenzymes; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D020928:Mitogen-Activated Protein Kinases; D000254:Sodium-Potassium-Exchanging ATPase; D004298:Dopamine