A novel role for protein phosphatase 2A in the dopaminergic regulation of Na,K-ATPase.
Stimulation of dopaminergic type 1 (D(1)) receptors increases lung edema clearance by regulating Na,K-ATPase function in the alveolar epithelium. We studied the role of serine/threonine protein phosphatases in the Na,K-ATPase regulation by D(1) agonists in A549 cells. We found that low doses of the type 1/2A protein phosphatase inhibitor okadaic acid as well as SV40 small t antigen transiently transfected into A549 cells prevented the D(1) agonist-induced increase in Na,K-ATPase activity and translocation from intracellular pools to the plasma membrane. This was associated with a rapid and transient increase in protein phosphatase 2A activity. We conclude that D(1) stimulation regulates Na,K-ATPase activity by promoting recruitment of Na,K-ATPases from intracellular pools into the basolateral membranes of A549 cells via a type 2A protein phosphatase.
Lecuona
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Division of Pulmonary and Critical Care Medicine, Northwestern University, 300 East Superior Street, Tarry Building 14-707, Chicago, IL 60611, USA.
Garcia
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Sznajder
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D000957:Antigens, Viral, Tumor / Q000502:physiology; D001693:Biological Transport, Active / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology; D005277:Fenfluramine / Q000494:pharmacology; D006801:Humans; D019319:Okadaic Acid / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000502:physiology*; D054648:Protein Phosphatase 2; D011650:Pulmonary Alveoli / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D017447:Receptors, Dopamine D1 / Q000819:agonists; D013539:Simian virus 40 / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D000957:Antigens, Viral, Tumor; D018491:Dopamine Agonists; D004791:Enzyme Inhibitors; D017447:Receptors, Dopamine D1; D019319:Okadaic Acid; D005277:Fenfluramine; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D000254:Sodium-Potassium-Exchanging ATPase; D004298:Dopamine