Dopamine D₁-like receptors regulate the α_1A-adrenergic receptor in human renal proximal tubule cells and D₁-like dopamine receptor knockout mice

Authors

Riley Charles Ennis, Thomas Jefferson High School for Science and Technology
Laureano D. Asico, University of Maryland School of Medicine
Ines Armando, University of Maryland School of Medicine
Jian Yang, University of Maryland School of Medicine
Jun B. Feranil, University of Maryland School of Medicine
Julie A. Jurgens, University of Maryland School of Medicine
Crisanto S. Escano, University of Maryland School of Medicine
Peiying Yu, University of Maryland School of Medicine
Xiaoyan Wang, University of Maryland School of Medicine
David R. Sibley, National Institute of Neurological Disorders and Stroke (NINDS)
Pedro A. Jose, University of Maryland School of Medicine
Van Anthony M. Villar, University of Maryland School of Medicine

Document Type

Journal Article

Publication Date

1-1-2014

Journal

American Journal of Physiology - Renal Physiology

Volume

307

Issue

11

DOI

10.1152/ajprenal.00119.2014

Keywords

Adrenergic receptor; Dopamine receptor; Knockout mice; Renal proximal tubule cells; Sodium transport

Abstract

© 2014 the American Physiological Society. The homeostatic control of blood pressure hinges upon the delicate balance between prohypertensinogenic and antihypertensinogenic systems. D1-like dopamine receptors [dopamine D1 and D5 receptors (D1Rs and D5Rs, respectively)] and the a1A-adrenergic receptor (α1A-AR) are expressed in the renal proximal tubule and engender opposing effects on Na+ transport, i.e., natriuresis (via D1Rs and D5Rs) or antinatriuresis (via α1A-ARs). We tested the hypothesis that the D1R/D5R regulates the α1A-AR. D1-like dopamine receptors coimmunoprecipitated, colocalized, and cofractionated with ct1A-ARs in lipid rafts in immortalized human renal proximal tubule cells. Long-term treatment with the D1R/D5R agonist fenoldopam resulted in decreased D1R and D5R expression but increased α1A-AR abundance in the plasma membrane. Short-term fenoldopam treatment stimulated the translocation of Na+-K+-ATPase from the plasma membrane to the cytosol that was partially reversed by an α1A-AR agonist, which by itself induced Na+-K+-ATPase translocation from the cytosol to the plasma membrane. The a1A-AR-specific agonist A610603 also minimized the ability of fenoldopam to inhibit Na+-K+-ATPase activity. To determine the interaction among D1Rs, D5Rs, and α1A-ARs in vivo, we used phenylephrine and A610603 to decrease Na+ excretion in several D1-like dopamine receptor knockout mouse strains. Phenylephrine and A61603 treatment resulted in a partial reduction of urinary Na+ excretion in wild-type mice and its abolition in D1R knockout, D5R knockout, and D1R-D5R double-knockout mice. Our results demonstrate the ability of the D1-like dopamine receptors to regulate the expression and activity of α1A-AR. Elucidating the intricacies of the interaction among these receptors is crucial for a better understanding of the crosstalk between anti- and pro-hypertensive systems.

APA Citation

Ennis, R., Asico, L., Armando, I., Yang, J., Feranil, J., Jurgens, J., Escano, C., Yu, P., Wang, X., Sibley, D., Jose, P., & Villar, V. (2014). Dopamine D₁-like receptors regulate the α_1A-adrenergic receptor in human renal proximal tubule cells and D₁-like dopamine receptor knockout mice. American Journal of Physiology - Renal Physiology, 307 (11). http://dx.doi.org/10.1152/ajprenal.00119.2014