FIG. 5.

Regulation of D₁R by GRK4 in the kidney. The increased expression and activity of GRK4 and its GRK4 gene variants (R65L, A142V, and A486V) cause D₁R phosphorylation and D₁R/G protein uncoupling, followed with inactivity of D₁R and increased the activity of NADPH oxidases, leading to the increased ROS production and blood pressure. The broken lines indicate inhibitory effects, whereas the solid lines indicate stimulatory effects. D₁R, dopamine receptor type 1; GRK4, G protein-coupled receptor kinase 4.