Characterization of acute inhibition of Na/H exchanger NHE-3 by dopamine in opossum kidney cells

M. R. Wiederkehr, F. Di Sole, R. Collazo, H. Quiñones, L. Fan, H. Murer, C. Helmle-Kolb, O. W. Moe

Research output: Contribution to journalArticle

48 Scopus citations

Abstract

Background. Dopamine (DA) is a principal natriuretic hormone that defends extracellular fluid volume from a Na load. Natriuresis is effected partly through inhibiting the proximal tubule Na/H exchanger NHE-3. Changes in NHE-3 phosphorylation is one mechanism by which NHE-3 activity is regulated. Methods. We used opossum kidney (OK) cells to characterize the differential and synergistic effects of DA receptor subtype-1 (DA1) and -2 (DA2) agonists and the effect of blockade of protein kinase A (PKA) or protein kinase C (PKC) on NHE-3 activity and phosphorylation. Results. DA and DA1 agonists inhibited NHE-3 activity, and DA1 antagonist blocked the effect of either DA or DA1 agonist. DA2 agonist alone had no effect, but DA2 antagonist reduced the DA effect on NHE-3 activity. DA1 and DA2 agonists together were more potent than DA1 alone. PKA inhibition eliminated the effect of DA1 agonist and partially blocked the effect of DA on NHE-3 activity. PKC inhibition did not block the DA effect. DA1 agonist and PKA activation phosphorylated NHE-3 on identical sites. Despite lack of effect on NHE-3 activity, DA2 agonists increased NHE-3 phosphorylation. DA-induced NHE-3 phosphorylation was distinct from DA1 and PKA but closely resembled DA2. Conclusion. We postulate the following: (1) DA modifies NHE-3 phosphorylation by activating PKA through DA1 and by other kinases/phosphatases via DA2. (2) DA1 is sufficient to inhibit NHE-3, while DA2 is insufficient but plays a synergistic role by altering NHE-3 phosphorylation.

Original languageEnglish (US)
Pages (from-to)197-209
Number of pages13
JournalKidney international
Volume59
Issue number1
DOIs
StatePublished - Jan 1 2001

Keywords

  • Dopamine receptors
  • Natriuresis
  • Phosphorylation
  • Protein kinase
  • Proximal tubule

ASJC Scopus subject areas

  • Nephrology

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