Dopamine D2L receptors stimulate Na+/K(+)-ATPase activity in murine LTK- cells.
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 microM, 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.
Yamaguchi
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I
Department of Pathology, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Walk
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SF
Jose
P A
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Felder
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RA
D000262:Adenylyl Cyclases / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D016048:Dideoxyadenosine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D004873:Ergolines / Q000494:pharmacology; D007700:Kinetics; D007739:L Cells; D051379:Mice; D010042:Ouabain / Q000494:pharmacology; D037342:Pertussis Toxin; D019257:Quinpirole; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D012413:Rubidium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013134:Spiperone / Q000378:metabolism; D014162:Transfection; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D018491:Dopamine Agonists; D004873:Ergolines; D017448:Receptors, Dopamine D2; D011994:Recombinant Proteins; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D019257:Quinpirole; D016048:Dideoxyadenosine; D013134:Spiperone; D010042:Ouabain; D000242:Cyclic AMP; D037342:Pertussis Toxin; D000262:Adenylyl Cyclases; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium