PTH and DA regulate Na-K ATPase through divergent pathways

Syed Jalal Khundmiri, Eleanor Lederer

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

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 a-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.

Original languageEnglish (US)
Pages (from-to)F512-F522
JournalAmerican Journal of Physiology - Renal Physiology
Volume282
Issue number3 51-3
DOIs
StatePublished - 2002
Externally publishedYes

Keywords

  • Extracellular signal-regulated kinase
  • Opossum kidney cells
  • Phospholipase A
  • Protein kinase A
  • Protein kinase C

ASJC Scopus subject areas

  • Physiology
  • Urology

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