title: Inhibitory effect of D1-like dopamine receptors on neuropeptide Y-induced proliferation in vascular smooth muscle cells.
abstract: Proliferation of vascular smooth muscle cells (VSMCs) is thought to have a key role in the development of atherosclerotic lesions. Neuropeptide Y (NPY), norepinephrine and dopamine are sympathetic neurotransmitters. NPY has been particularly shown to stimulate proliferation of VSMCs. NPY, norepinephrine and dopamine are all sympathetic transmitters. In our previous study, we found that in the presence of the dopamine receptor, the α1-adrenergic receptor-mediated VSMC proliferation is reduced. We hypothesize that the activation of the D1-like receptor might inhibit the NPY-mediated VSMC proliferation. In our present study, we found that NPY, mainly via the Y1 receptor, increased VSMC proliferation. This was determined by [(3)H]-thymidine incorporation, in a concentration (10(-11) to 10(-8)  M)-dependent manner. In the presence of the D1-like receptor agonist, fenoldopam (10(-12) to 10(-5) M), the stimulatory effect of NPY on VSMC proliferation was reduced. The involvement of the D1-like receptor was confirmed when the inhibitory effect of fenoldopam was reversed in the presence of the D1-like receptor antagonist SCH-23390 (10(-8) M). Moreover, the inhibitory effect of fenoldopam on NPY-mediated VSMC proliferation was also blocked in the presence of the PKA inhibitor 14-22 (10(-6)  M). Protein kinase A activator 8-(4-chlorophenylthio) adenosine-3,5-cyclic monophosphorothioate, Sp-isomer sodium salt (10(-6)  M) could simulate the stimulatory effect of fenoldopam. It indicated that the inhibitory effect of D1-like receptors on NPY-mediated VSMC proliferation may have an important role in the regulation of blood pressure or prevention of atherosclerosis.
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, China.|Chongqing Institute of Cardiology, Chongqing, China.|Department of Cardiology, The First Affiliated Hospital of Shantou University Medical College, Shantou, China.
authors.forename: Yongqiao
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, China.|Chongqing Institute of Cardiology, Chongqing, China.
authors.forename: Weibin
authors.initials: W
authors.lastname: Shi
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, China.|Chongqing Institute of Cardiology, Chongqing, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Luo
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, China.|Chongqing Institute of Cardiology, Chongqing, China.
authors.forename: Rongchuan
authors.initials: R
authors.lastname: Yue
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, China.|Chongqing Institute of Cardiology, Chongqing, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, China.|Chongqing Institute of Cardiology, Chongqing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, China.|Chongqing Institute of Cardiology, Chongqing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, China.|Chongqing Institute of Cardiology, Chongqing, China.
authors.forename: Wei Eric
authors.initials: WE
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, China.|Chongqing Institute of Cardiology, Chongqing, China.
authors.forename: Hongyong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, China.|Chongqing Institute of Cardiology, Chongqing, China.
authors.forename: Chunyu
authors.initials: C
authors.lastname: Zeng
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000209:etiology; D049109:Cell Proliferation / Q000187:drug effects; D017868:Cyclic AMP-Dependent Protein Kinases / Q000502:physiology; D018818:Fenoldopam / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000502:physiology; D058426:Neointima; D009478:Neuropeptide Y / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000502:physiology*
chemical_list: D009478:Neuropeptide Y; D017447:Receptors, Dopamine D1; D017868:Cyclic AMP-Dependent Protein Kinases; D018818:Fenoldopam