Dopamine D^sub 1^-like receptors regulate the [alpha]^sub 1A^-adrenergic receptor in human renal proximal tubule cells and D^sub 1^-like dopamine receptor knockout mice

• Published in: American journal of physiology. Renal physiology Vol. 307; no. 11; p. F1238
• Main Authors: Ennis, Riley Charles, Asico, Laureano D, Armando, Ines, Yang, Jian, Feranil, Jun B, Jurgens, Julie A, Escano, Crisanto S, Yu, Peiying, Wang, Xiaoyan, Sibley, David R, Jose, Pedro A, Villar, Van Anthony M
• Format: Journal Article
• Language: English
• Published: Bethesda American Physiological Society 01.12.2014
• Subjects: Blood pressure; Cells; Dopamine; Homeostasis; Kidneys; Rodents
• ISSN: 1931-857X

The homeostatic control of blood pressure hinges upon the delicate balance between prohypertensinogenic and antihypertensinogenic systems. D1-like dopamine receptors [dopamine D... and D... receptors (D...Rs and D...Rs, respectively)] and the α...-adrenergic receptor (α...-AR) are expressed in the renal proximal tubule and engender opposing effects on Na+ transport, i.e., natriuresis (via D...Rs and D...Rs) or antinatriuresis (via α...-ARs). We tested the hypothesis that the D...R/D...R regulates the α...-AR. D...-like dopamine receptors coimmunoprecipitated, colocalized, and cofractionated with α...-ARs in lipid rafts in immortalized human renal proximal tubule cells. Long-term treatment with the D...R/D...R agonist fenoldopam resulted in decreased D1R and D5R expression but increased α...-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 α...-AR agonist, which by itself induced Na+-K+-ATPase translocation from the cytosol to the plasma membrane. The α...-AR-specific agonist A610603 also minimized the ability of fenoldopam to inhibit Na+-K+-ATPase activity. To determine the interaction among D...Rs, D...Rs, and α...-ARs in vivo, we used phenylephrine and A610603 to decrease Na+ excretion in several D...-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 D...R knockout, D...R knockout, and D1R-D5R double-knockout mice. Our results demonstrate the ability of the D...-like dopamine receptors to regulate the expression and activity of α...-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. (ProQuest: ... denotes formulae/symbols omitted.)