Dopamine D 1 Receptor Augmentation of D 3 Receptor Action in Rat Aortic or Mesenteric Vascular Smooth Muscles

Abstract

Dopamine is an important modulator of blood pressure, in part, by regulating vascular resistance. To test the hypothesis that D 1 and D 3 receptors interact in vascular smooth muscle cells, we studied A10 cells, a rat aortic smooth muscle cell line, and rat mesenteric arteries that express both dopamine receptor subtypes. Fenoldopam, a D 1 -like receptor agonist, increased both D 1 and D 3 receptor protein in a time-dependent and a concentration-dependent manner in A10 cells. The effect of fenoldopam was specific because a D 1 -like receptor antagonist, SCH23390 (10 −7 M/24 h), completely blocked the stimulatory effect of fenoldopam (10 −7 M/24 h) (D 3 receptor: control=21±1 density units [DU]); SCH23390=23±2 DU; fenoldopam=33±2 DU; fenoldopam+SCH23390=23±2 DU; n=10). D 1 and D 3 receptors physically interacted with each other because fenoldopam (10 −7 M/24 h) increased D 1 /D 3 receptor coimmunoprecipitation (35±5 versus 65±5 DU; n=8). A D 3 receptor agonist, PD128907, relaxed mesenteric arterial rings independent of the endothelium, effects that were blocked by a D 3 receptor antagonist, U99194A. Costimulation of D 1 and D 3 receptors led to additive vasorelaxation. We conclude that the D 1 receptor regulates the D 3 receptor by physical interaction and receptor expression. D 1 receptor stimulation augments D 3 receptor vasorelaxant effects. An interaction of D 1 and D 3 receptors may be involved in the regulation of blood pressure.