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2 Veterans Administration and Department of Medicine1,2, University of Louisville, School of Medicine, Louisville, Kentucky 40202
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 A2 (PLA2)-dependent pathways and
the late inhibition through protein kinase A- and
PLA2-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
-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.
protein kinase A; protein kinase C; phospholipase A2; opossum kidney cells; extracellular signal-regulated kinase
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