title: Inhibitory effect of D1-like and D3 dopamine receptors on norepinephrine-induced proliferation in vascular smooth muscle cells.
abstract: 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.
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.forename: Changqing
authors.initials: C
authors.lastname: Yu
authors.forename: Yu
authors.initials: Y
authors.lastname: Han
authors.forename: Hongmei
authors.initials: H
authors.lastname: Ren
authors.forename: Weibin
authors.initials: W
authors.lastname: Shi
authors.forename: Chunjiang
authors.initials: C
authors.lastname: Fu
authors.forename: Duofen
authors.initials: D
authors.lastname: He
authors.forename: Lan
authors.initials: L
authors.lastname: Huang
authors.forename: Chengming
authors.initials: C
authors.lastname: Yang
authors.forename: Xukai
authors.initials: X
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.forename: Laureano D
authors.initials: LD
authors.lastname: Asico
authors.forename: Chunyu
authors.initials: C
authors.lastname: Zeng
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Jose
mesh_terms: 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
chemical_list: 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