PTH and DA regulate Na-K ATPase through divergent pathways.
Parathyroid hormone (PTH) and dopamine (DA) inhibit Na-K ATPase activity and sodium-phosphate cotransport in proximal tubular cells. We previously showed that PTH and DA inhibit phosphate transport in opossum kidney (OK) cells through different signaling pathways. Therefore, we hypothesized that PTH and DA also inhibit Na-K ATPase through divergent pathways. We measured PTH and DA inhibition of Na-K ATPase activity in the presence of inhibitors of signaling pathways. PTH and DA inhibited Na-K ATPase in a biphasic manner, the early inhibition through protein kinase C (PKC)- and phospholipase A(2) (PLA(2))-dependent pathways and the late inhibition through protein kinase A- and PLA(2)-dependent pathways. Inhibition of extracellular signal-regulated kinase (ERK) activation blocked early and late inhibition of Na-K ATPase by PTH but not by DA. Pertussis toxin blocked early and late inhibition by DA but not by PTH. Treatment with DA, but not PTH, resulted in an early downregulation of basolateral membrane expression of the alpha-subunit, whereas total cellular expression remained constant for both agonists. We conclude that PTH and DA regulate Na-K ATPase by different mechanisms through activation of divergent pathways.
Khundmiri
Syed Jalal
SJ
Veterans Administration and Department of Medicine, University of Louisville, School of Medicine, Louisville, Kentucky 40202, USA.
Lederer
Eleanor
E
D000818:Animals; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D007668:Kidney / Q000166:cytology / Q000201:enzymology*; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D009281:Naphthalenes / Q000494:pharmacology; D009893:Opossums; D010281:Parathyroid Hormone / Q000494:pharmacology*; D037342:Pertussis Toxin; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010741:Phospholipases A / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D011753:Pyrones / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013449:Sulfonamides; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007546:Isoquinolines; D009281:Naphthalenes; D010281:Parathyroid Hormone; D010726:Phosphodiesterase Inhibitors; D011753:Pyrones; D013449:Sulfonamides; D010566:Virulence Factors, Bordetella; C061465:calphostin complex; C068314:6-(bromomethylene)tetrahydro-3-(1-naphthaleneyl)-2H-pyran-2-one; D037342:Pertussis Toxin; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D010741:Phospholipases A; D000254:Sodium-Potassium-Exchanging ATPase; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D004298:Dopamine