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
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 r...
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Published in | American journal of physiology. Renal physiology Vol. 307; no. 11; p. F1238 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Bethesda
American Physiological Society
01.12.2014
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Subjects | |
Online Access | Get full text |
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Summary: | 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.) |
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ISSN: | 1931-857X 1522-1466 |