The Dopamine D1‐like Receptors Interact with the α1A Adrenergic Receptor in Human Renal Epithelial Tubule Cells

Abstract

As a multifactorial disorder, essential hypertension is influenced not just by the individual's lifestyle and environment but also by the interplay of a myriad of physiologic systems that either promote or protect against sustained increase in blood pressure. The D1-like dopamine receptors (D1R and D5R) and the α1A adrenergic receptor (ARα1A) are endogenously expressed in the kidney and promote contrasting effects on sodium transport, resulting in natriuresis (D1R and D5R) or anti-natriuresis (ARα1A). We tested the hypothesis that the D1R and D5R interact with ARα1A in human renal proximal tubule cells (hPTCs). We found that D1R and D5R co-immunoprecipitated endogenous ARα1A and pulled-down heterologous ARα1A-myc,His and that treatment with the D1-like receptor agonist fenoldopam (1μM/10 min) enhanced the interaction. D1R and D5R also colocalized with ARα1A in HEK293 cells, in which fenoldopam increased their colocalization at the perinuclear area, and in proximal tubules (and distal tubules for D5R) in human kidney sections. Prolonged (24-hr) fenoldopam treatment resulted in decreased D1R (70.0±5.9% vs. 100±3.7%, P<0.05, n=3) and D5R (50.1±10.7% vs. 100±10.7%, P<0.05, n=3) and increased ARα1A abundance (142.6±4.3% vs. 100±6.4%, P<0.05, n=3) in hPTCs, suggesting that the D1-like dopamine receptors may regulate the expression of ARα1A. Understanding the interaction between these receptors is essential to comprehending the crosstalk between anti- and pro-hypertensive systems.