Inhibition of Na,K-ATPase by Dopamine in Proximal Tubule Epithelial Cells

In the current report we review the results that lay grounds for the model of intracellular sodium-mediated dopamine-induced endocytosis of Na,K-ATPase. Under conditions of a high salt diet, dopamine activates PKCζ, which phosphorylates NKA α1 Ser-18. The phosphorylation produces a conformational change of α1 NH2-terminus, which through interaction with other domains of α1 exposes PI3K- and AP-2-binding domains. PI3K bound to the NKA α1 induces the recruitment and activation of other proteins involved in endocytosis, and PI3K-generated 3-phosphoinositides affect the local cytoskeleton and modify the biophysical conditions of the membrane for development of clathrin-coated pits. Plasma membrane phosphorylated NKA is internalized to specialized intracellular compartments where the NKA will be dephosphorylated. The NKA internalization results in a reduced Na+ transport by proximal tubule epithelial cells.