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 PKCzeta, which phosphorylates NKA alpha1 Ser-18. The phosphorylation produces a conformational change of alpha1 NH2-terminus, which through interaction with other domains of alpha1 exposes PI3K- and AP-2-binding domains. PI3K bound to the NKA alpha1 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.
Pedemonte
Carlos H
CH
College of Pharmacy, University of Houston, Houston, TX 77204, USA. cpedemonte@uh.edu
Efendiev
Riad
R
Bertorello
Alejandro M
AM
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004298:Dopamine / Q000494:pharmacology*; D004705:Endocytosis / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology*; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology*; D046912:Multiprotein Complexes / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000187:drug effects* / Q000378:metabolism; D033921:Vesicular Transport Proteins / Q000187:drug effects / Q000378:metabolism
D002316:Cardiotonic Agents; D046912:Multiprotein Complexes; D033921:Vesicular Transport Proteins; D011493:Protein Kinase C; D000254:Sodium-Potassium-Exchanging ATPase; D004298:Dopamine