Dopamine regulation of Na+-K+-ATPase requires the PDZ-2 domain of sodium hydrogen regulatory factor-1 (NHERF-1) in opossum kidney cells

Sarah Salyer, Nina Lesousky, Edward J. Weinman, Barbara J. Clark, Eleanor D. Lederer, Syed J. Khundmiri

Research output: Contribution to journalArticle

Abstract

Na+-K+-ATPase activity in renal proximal tubule is regulated by several hormones including parathyroid hormone (PTH) and dopamine. The current experiments explore the role of Na+/H+ exchanger regulatory factor 1 (NHERF-1) in dopamine-mediated regulation of Na+-K+-ATPase. We measured dopamine regulation of ouabain-sensitive 86Rb uptake and Na+-K+-ATPase α1 subunit phosphorylation in wild-type opossum kidney (OK) (OK-WT) cells, OKH cells (NHERF-1-deficient), and OKH cells stably transfected with full-length human NHERF-1 (NF) or NHERF-1 constructs with mutated PDZ-1 (Z1) or PDZ-2 (Z2) domains. Treatment with 1 μM dopamine decreased ouabain-sensitive 86Rb uptake, increased phosphorylation of Na+-K +-ATPase α1-subunit, and enhanced association of NHERF-1 with D1 receptor in OK-WT cells but not in OKH cells. Transfection with wild-type, full-length, or PDZ-1 domain-mutated NHERF-1 into OKH cells restored dopamine-mediated regulation of Na+-K+-ATPase and D1-like receptor association with NHERF-1. Dopamine did not regulate Na +-K+-ATPase or increase D1-like receptor association with NHERF-1 in OKH cells transfected with mutated PDZ-2 domain. Dopamine stimulated association of PKC-ζ with NHERF-1 in OK-WT and OKH cells transfected with full-length or PDZ-1 domain-mutated NHERF-1 but not in PDZ-2 domain-mutated NHERF-1-transfected OKH cells. These results suggest that NHERF-1 mediates Na+-K+-ATPase regulation by dopamine through its PDZ-2 domain.

Original languageEnglish (US)
Pages (from-to)C425-C434
JournalAmerican Journal of Physiology - Cell Physiology
Volume300
Issue number3
DOIs
StatePublished - Mar 2011
Externally publishedYes

Keywords

  • D1 receptor
  • Oximal tubule
  • Pkc-ζ
  • Sodium homeostasis

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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