title: Agonist-dependent regulation of renal Na+,K+-ATPase activity is modulated by intracellular sodium concentration.
abstract: We tested the hypothesis that the level of intracellular sodium modulates the hormonal regulation of the Na(+),K(+)-ATPase activity in proximal tubule cells. By using digital imaging fluorescence microscopy of a sodium-sensitive dye, we determined that the sodium ionophore monensin induced a dose-specific increase of intracellular sodium. A correspondence between the elevation of intracellular sodium and the level of dopamine-induced inhibition of Na(+),K(+)-ATPase activity was determined. At basal intracellular sodium concentration, stimulation of cellular protein kinase C by phorbol 12-myristate 13-acetate (PMA) promoted a significant increase in Na(+),K(+)-ATPase activity; however, this activation was gradually reduced as the concentration of intracellular sodium was increased to become a significant inhibition at concentrations of intracellular sodium higher than 16 mm. Under these conditions, PMA and dopamine share the same signaling pathway to inhibit the Na(+),K(+)-ATPase. The effects of PMA and dopamine on the Na(+),K(+)-ATPase activity and the modulation of these effects by different intracellular sodium concentrations were not modified when extracellular and intracellular calcium were almost eliminated. These results suggest that the level of intracellular sodium modulates whether hormones stimulate, inhibit, or have no effect on the Na(+),K(+)-ATPase activity leading to a tight control of sodium reabsorption.
authors.affiliation: College of Pharmacy, University of Houston, Houston, Texas 77204, USA.
authors.forename: Riad
authors.initials: R
authors.lastname: Efendiev
authors.forename: Alejandro M
authors.initials: AM
authors.lastname: Bertorello
authors.forename: Ruben
authors.initials: R
authors.lastname: Zandomeni
authors.forename: Angel R
authors.initials: AR
authors.lastname: Cinelli
authors.forename: Carlos H
authors.initials: CH
authors.lastname: Pedemonte
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D004298:Dopamine / Q000494:pharmacology; D004789:Enzyme Activation; D007668:Kidney / Q000201:enzymology*; D008985:Monensin / Q000494:pharmacology; D009893:Opossums; D009994:Osmolar Concentration; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D008985:Monensin; D012964:Sodium; D011493:Protein Kinase C; D000254:Sodium-Potassium-Exchanging ATPase; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; D004298:Dopamine