title: Dopamine D₁-like receptors regulate the α₁A-adrenergic receptor in human renal proximal tubule cells and D₁-like dopamine receptor knockout mice.
abstract: 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.
authors.affiliation: Thomas Jefferson High School for Science and Technology, Alexandria, Virgina;
authors.forename: Riley Charles
authors.initials: RC
authors.lastname: Ennis
authors.affiliation: Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland;
authors.forename: Laureano D
authors.initials: LD
authors.lastname: Asico
authors.affiliation: Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland;
authors.forename: Ines
authors.initials: I
authors.lastname: Armando
authors.affiliation: Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland;
authors.forename: Jian
authors.initials: J
authors.lastname: Yang
authors.affiliation: Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland;
authors.forename: Jun B
authors.initials: JB
authors.lastname: Feranil
authors.affiliation: Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland;
authors.forename: Julie A
authors.initials: JA
authors.lastname: Jurgens
authors.affiliation: Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland;
authors.forename: Crisanto S
authors.initials: CS
authors.lastname: Escano
authors.affiliation: Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland;
authors.forename: Peiying
authors.initials: P
authors.lastname: Yu
authors.affiliation: Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland;
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.affiliation: Molecular Neuropharmacology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland;
authors.forename: David R
authors.initials: DR
authors.lastname: Sibley
authors.affiliation: Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland; Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Jose
authors.affiliation: Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland; vvillar@medicine.umaryland.edu.
authors.forename: Van Anthony M
authors.initials: VA
authors.lastname: Villar
mesh_terms: D000818:Animals; D019921:Biotinylation; D001794:Blood Pressure / Q000502:physiology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018340:Receptors, Adrenergic, alpha-1 / Q000096:biosynthesis*; D017447:Receptors, Dopamine D1 / Q000235:genetics* / Q000502:physiology*; D050641:Receptors, Dopamine D5 / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D018340:Receptors, Adrenergic, alpha-1; D017447:Receptors, Dopamine D1; D050641:Receptors, Dopamine D5; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase
keywords: adrenergic receptor; dopamine receptor; knockout mice; renal proximal tubule cells; sodium transport