title: PKC-beta and PKC-zeta mediate opposing effects on proximal tubule Na+,K+-ATPase activity.
abstract: Dopamine (DA) inhibits rodent proximal tubule Na+,K+-ATPase via stimulation of protein kinase C (PKC). However, direct stimulation of PKC by phorbol 12-myristate 13-acetate (PMA) results in increased Na+,K+-ATPase. LY333531, a specific inhibitor of the PKC-beta isoform, prevents PMA-dependent activation of Na+,K+-ATPase, but has no effect on DA inhibition of this activity. A similar result was obtained with a PKC-beta inhibitor peptide. Concentrations of staurosporine, that inhibits PKC-zeta, prevent DA-dependent inhibition of Na+,K+-ATPase and a similar effect was obtained with a PKC-zeta inhibitor peptide. Thus, PMA-dependent stimulation of Na+,K+-ATPase is mediated by activation of PKC-beta, whereas inhibition by DA requires activation of PKC-zeta.
authors.affiliation: College of Pharmacy, University of Houston, TX 77204-5515, USA.
authors.forename: R
authors.initials: R
authors.lastname: Efendiev
authors.forename: A M
authors.initials: AM
authors.lastname: Bertorello
authors.forename: C H
authors.initials: CH
authors.lastname: Pedemonte
mesh_terms: D000818:Animals; D004298:Dopamine / Q000378:metabolism / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000201:enzymology*; D008301:Maleimides / Q000494:pharmacology; D009893:Opossums; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D064546:Protein Kinase C beta; D012413:Rubidium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D007527:Isoenzymes; D008301:Maleimides; D010455:Peptides; C099154:ruboxistaurin; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D000254:Sodium-Potassium-Exchanging ATPase; D019311:Staurosporine; D012413:Rubidium; D013755:Tetradecanoylphorbol Acetate; D004298:Dopamine