Inhibitory effect of D1-like and D3 dopamine receptors on norepinephrine-induced proliferation in vascular smooth muscle cells.
The sympathetic nervous system plays an important role in the regulation of blood pressure. There is increasing evidence for positive and negative interactions between dopamine and adrenergic receptors; the activation of the alpha-adrenergic receptor induces vasoconstriction, whereas the activation of dopamine receptor induces vasorelaxation. We hypothesize that the D1-like receptor and/or D3 receptor also inhibit alpha1-adrenergic receptor-mediated proliferation in vascular smooth muscle cells (VSMCs). In this study, VSMC proliferation was determined by measuring [3H]thymidine incorporation, cell number, and uptake of 3-(4,5-dimethylthiazol-2-yl)-diphenyltetrazolium bromide (MTT). Norepinephrine increased VSMC number and MTT uptake, as well as [3H]thymidine incorporation via the alpha1-adrenergic receptor in aortic VSMCs from Sprague-Dawley rats. The proliferative effects of norepinephrine were attenuated by the activation of D1-like receptors or D3 receptors, although a D1-like receptor agonist, fenoldopam, and a D3 receptor agonist, PD-128907, by themselves, at low concentrations, had no effect on VSMC proliferation. Simultaneous stimulation of both D1-like and D3 receptors had an additive inhibitory effect. The inhibitory effect of D3 receptor was via protein kinase A, whereas the D1-like receptor effect was via protein kinase C-zeta. The interaction between alpha1-adrenergic and dopamine receptors, especially D1-like and D3 receptors in VSMCs, could be involved in the pathogenesis of hypertension.
Li
Zhen
Z
Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, People's Republic of China.
Yu
Changqing
C
Han
Yu
Y
Ren
Hongmei
H
Shi
Weibin
W
Fu
Chunjiang
C
He
Duofen
D
Huang
Lan
L
Yang
Chengming
C
Wang
Xukai
X
Zhou
Lin
L
Asico
Laureano D
LD
Zeng
Chunyu
C
Jose
Pedro A
PA
D058646:Adrenergic alpha-1 Receptor Agonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001578:Benzopyrans / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018818:Fenoldopam / Q000494:pharmacology; D018832:Molecular Chaperones / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D010078:Oxazines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism*; D000099221:Protein Kinase C zeta
D058646:Adrenergic alpha-1 Receptor Agonists; D000317:Adrenergic alpha-Antagonists; D001578:Benzopyrans; D017868:Cyclic AMP-Dependent Protein Kinases; D018491:Dopamine Agonists; D018818:Fenoldopam; D018832:Molecular Chaperones; D009638:Norepinephrine; D010078:Oxazines; D011224:Prazosin; D018340:Receptors, Adrenergic, alpha-1; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C490392:Prkcz protein, rat; D000099221:Protein Kinase C zeta; C062458:3,4,4a,10b-tetrahydro-4-propyl-2H,5H-(1)benzopyrano(4,3-b)-1,4-oxazin-9-ol