Dopamine D2L receptors stimulate Na+/K+-ATPase activity in murine LTK- cells

Ikuyo Yamaguchi, Scott F. Walk, Pedro A. Jose, Robin A. Felder

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

Ion transport can be regulated by dopamine receptors. D1-like receptors inhibit both Na+/H+ exchange (NHE) and Na+/K+-ATPase activity, whereas D2-like receptors stimulate NHE. However, the effect of D2-like receptors on Na+/K+-ATPase activity is controversial. In renal proximal tubular cells, where several D1-like and D2-like receptors are expressed, D2 agonists have been reported either to have no effect or to act in concert with D1 agonists to inhibit Na+/K+-ATPase activity. We therefore studied the effect of D2 receptors on Na+/K+-ATPase activity in LTK- cells transfected with a rat D2Long receptor cDNA (maximum receptor density = 0.91 ± 0.26 pmol/mg protein, dissociation constant = 2.39 ± 0.79 nM, seven experiments). The activation of D2 receptors in these transfected cells by the selective D2 agonist LY171555 led to the inhibition of forskolin-stimulated CAMP accumulation. In the D2Long-transfected, but not in nontransfected cells, LY171555 caused a concentration-dependent stimulation of Na+/K+-ATPase activity (EC50 = 0.55 ± 0.2 μM, Emax = 28 ± 6%, six experiments), which was completely blocked by the D2-selective antagonist (-)-sulpiride. The D2-stimulated Na+/K+-ATPase activity was not secondary to D2 receptor activation of K+ channels or NHE activity since LY171555 stimulated Na+/K+-ATPase activity in D2Long-transfected cells, even when K+ channels were blocked by CsCl and intracellular Na+ was clamped by monensin. The D2-stimulated Na+/K+-ATPase activity was blocked by pertussis toxin and mimicked by dideoxyadenosine. We conclude that agonist occupancy of D2Long dopamine receptors stimulates Na+/K+-ATPase activity; this effect is mediated by the inhibition of cAMP production and is independent of intracellular Na+ and K+ concentration.

Original languageEnglish (US)
Pages (from-to)373-378
Number of pages6
JournalMolecular pharmacology
Volume49
Issue number2
StatePublished - Feb 1996
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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