title: Intracellular Na+ regulates dopamine and angiotensin II receptors availability at the plasma membrane and their cellular responses in renal epithelia.
abstract: The balance and cross-talk between natruretic and antinatruretic hormone receptors plays a critical role in the regulation of renal Na+ homeostasis, which is a major determinant of blood pressure. Dopamine and angiotensin II have antagonistic effects on renal Na+ and water excretion, which involves regulation of the Na+,K+-ATPase activity. Herein we demonstrate that angiotensin II (Ang II) stimulation of AT1 receptors in proximal tubule cells induces the recruitment of Na+,K+-ATPase molecules to the plasmalemma, in a process mediated by protein kinase Cbeta and interaction of the Na+,K+-ATPase with adaptor protein 1. Ang II stimulation led to phosphorylation of the alpha subunit Ser-11 and Ser-18 residues, and substitution of these amino acids with alanine residues completely abolished the Ang II-induced stimulation of Na+,K+-ATPase-mediated Rb+ transport. Thus, for Ang II-dependent stimulation of Na+,K+-ATPase activity, phosphorylation of these serine residues is essential and may constitute a triggering signal for recruitment of Na+,K+-ATPase molecules to the plasma membrane. When cells were treated simultaneously with saturating concentrations of dopamine and Ang II, either activation or inhibition of the Na+,K+-ATPase activity was produced dependent on the intracellular Na+ concentration, which was varied in a very narrow physiological range (9-19 mm). A small increase in intracellular Na+ concentrations induces the recruitment of D1 receptors to the plasma membrane and a reduction in plasma membrane AT1 receptors. Thus, one or more proteins may act as an intracellular Na+ concentration sensor and play a major regulatory role on the effect of hormones that regulate proximal tubule Na+ reabsorption.
authors.affiliation: College of Pharmacy, University of Houston, Houston, Texas 77204, USA.
authors.forename: Riad
authors.initials: R
authors.lastname: Efendiev
authors.forename: Claudia E
authors.initials: CE
authors.lastname: Budu
authors.forename: Angel R
authors.initials: AR
authors.lastname: Cinelli
authors.forename: Alejandro M
authors.initials: AM
authors.lastname: Bertorello
authors.forename: Carlos H
authors.initials: CH
authors.lastname: Pedemonte
mesh_terms: D000042:Absorption; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology; D004847:Epithelial Cells; D006706:Homeostasis; D007668:Kidney; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D009893:Opossums; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D064546:Protein Kinase C beta; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D012413:Rubidium / Q000378:metabolism; D012694:Serine / Q000378:metabolism; D015398:Signal Transduction; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
chemical_list: D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D017447:Receptors, Dopamine D1; D000804:Angiotensin II; D012694:Serine; D012964:Sodium; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium; D013755:Tetradecanoylphorbol Acetate; D004298:Dopamine