Dopamine D₁-like receptors regulate the α₁A-adrenergic receptor in human renal proximal tubule cells and D₁-like dopamine receptor knockout mice

• Published in: American journal of physiology. Renal physiology 2014-12, Vol.307 (11), p.F1238-F1248
• Main Authors: Ennis, Riley Charles, Asico, Laureano D, Armando, Ines, Yang, Jian, Feranil, Jun B, Jurgens, Julie A, Escano, Jr, Crisanto S, Yu, Peiying, Wang, Xiaoyan, Sibley, David R, Jose, Pedro A, Villar, Van Anthony M
• Format: Article
• Language: English
• Subjects: Animals; Biotinylation; Blood Pressure - physiology; Cell Line; Cell Membrane - metabolism; Humans; Kidney Tubules, Proximal - cytology; Kidney Tubules, Proximal - metabolism; Mice; Mice, Knockout; Receptors, Adrenergic, alpha-1 - biosynthesis; Receptors, Dopamine D1 - genetics; Receptors, Dopamine D1 - physiology; Receptors, Dopamine D5 - metabolism; Sodium - metabolism; Sodium-Potassium-Exchanging ATPase - metabolism
• ISSN: 1931-857X; 1522-1466
• DOI: 10.1152/ajprenal.00119.2014

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 α₁A-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 α₁A-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 α₁A-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.