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

I Yamaguchi, SF Walk, PA Jose and RA Felder

Department of Pathology, University of Virginia Health Sciences Center, Charlottesville 22908, USA.

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.

Volume 49, Issue 2, pp. 373-378, 02/01/1996
Copyright © 1996 by American Society for Pharmacology and Experimental Therapeutics

This article has been cited by other articles:

				C. Zeng, I. Armando, Y. Luo, G. M. Eisner, R. A. Felder, and P. A. Jose Dysregulation of dopamine-dependent mechanisms as a determinant of hypertension: studies in dopamine receptor knockout mice Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H551 - H569. [Abstract] [Full Text] [PDF]

				P. Gomes and P. Soares-da-Silva D2-like receptor-mediated inhibition of Na+-K+-ATPase activity is dependent on the opening of K+ channels Am J Physiol Renal Physiol, July 1, 2002; 283(1): F114 - F123. [Abstract] [Full Text] [PDF]

				R. A. Felder, H. Sanada, J. Xu, P.-Y. Yu, Z. Wang, H. Watanabe, L. D. Asico, W. Wang, S. Zheng, I. Yamaguchi, et al. G protein-coupled receptor kinase 4 gene variants in human essential hypertension PNAS, March 19, 2002; 99(6): 3872 - 3877. [Abstract] [Full Text] [PDF]

				P. Gomes, M. A. Vieira-Coelho, and P. Soares-da-Silva Ouabain-insensitive acidification by dopamine in renal OK cells: primary control of the Na+/H+ exchanger Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2001; 281(1): R10 - R18. [Abstract] [Full Text] [PDF]

				A. G. Therien and R. Blostein Mechanisms of sodium pump regulation Am J Physiol Cell Physiol, September 1, 2000; 279(3): C541 - C566. [Abstract] [Full Text] [PDF]

				D. P. O'Connell, C. J. Vaughan, A. M. Aherne, S. J. Botkin, Z.-Q. Wang, R. A. Felder, and R. M. Carey Expression of the Dopamine D3 Receptor Protein in the Rat Kidney Hypertension, November 1, 1998; 32(5): 886 - 895. [Abstract] [Full Text] [PDF]

				P. A. Jose, L. D. Asico, G. M. Eisner, F. Pocchiari, C. Semeraro, and R. A. Felder Effects of costimulation of dopamine D1- and D2-like receptors on renal function Am J Physiol Regulatory Integrative Comp Physiol, October 1, 1998; 275(4): R986 - R994. [Abstract] [Full Text] [PDF]