| First Author | Ennis RC | Year | 2014 |
| Journal | Am J Physiol Renal Physiol | Volume | 307 |
| Issue | 11 | Pages | F1238-48 |
| PubMed ID | 25339698 | Mgi Jnum | J:216657 |
| Mgi Id | MGI:5609187 | Doi | 10.1152/ajprenal.00119.2014 |
| Citation | Ennis RC, et al. (2014) Dopamine D1-like receptors regulate the alpha1A-adrenergic receptor in human renal proximal tubule cells and D1-like dopamine receptor knockout mice. Am J Physiol Renal Physiol 307(11):F1238-48 |
| abstractText | 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 alpha1A-adrenergic receptor (alpha1A-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 alpha1A-ARs). We tested the hypothesis that the D1R/D5R regulates the alpha1A-AR. D1-like dopamine receptors coimmunoprecipitated, colocalized, and cofractionated with alpha1A-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 alpha1A-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 alpha1A-AR agonist, which by itself induced Na(+)-K(+)-ATPase translocation from the cytosol to the plasma membrane. The alpha1A-AR-specific agonist A610603 also minimized the ability of fenoldopam to inhibit Na(+)-K(+)-ATPase activity. To determine the interaction among D1Rs, D5Rs, and alpha1A-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 alpha1A-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. |
