Dopamine D1 receptor augmentation of D3 receptor action in rat aortic or mesenteric vascular smooth muscles.
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.
Zeng
Chunyu
C
Department of Pediatrics, PHC-2 Georgetown University Medical Center, 3800 Reservoir Road, NW, Washington, DC 20007, USA. cyzeng1@hotmail.com
Wang
Dan
D
Yang
Zhiwei
Z
Wang
Zheng
Z
Asico
Lareano D
LD
Wilcox
Christopher S
CS
Eisner
Gilbert M
GM
Welch
William J
WJ
Felder
Robin A
RA
Jose
Pedro A
PA
D000818:Animals; D000918:Antibody Specificity; D001011:Aorta / Q000166:cytology; D002460:Cell Line; D046508:Culture Techniques; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D018818:Fenoldopam / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000033:anatomy & histology / Q000737:chemistry / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011921:Rats, Inbred WKY; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000276:immunology / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000276:immunology / Q000378:metabolism*; D050637:Receptors, Dopamine D3; D014664:Vasodilation / Q000187:drug effects
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; C493595:Drd3 protein, rat; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D018818:Fenoldopam