title: Dopamine d(1)-like receptors suppress proliferation of vascular smooth muscle cell induced by insulin-like growth factor-1.
abstract: OBJECTIVE
  Proliferation of vascular smooth muscle cells (VSMCs) participates in the pathogenesis and development of cardiovascular diseases, including essential hypertension and atherosclerosis. Our previous study found that stimulation of D1-like dopamine receptors inhibited insulin-induced proliferation of VSMCs. Insulin-like growth factor-1 (IGF-1) and insulin share similar structure and biological effect. However, whether or not there is any effect of D1-like receptors on IGF-1-induced proliferation of VSMCs is not known. Therefore, we investigated the inhibitory effect of D1-like dopamine receptors on the IGF-1-induced VSMCs proliferation in this study.
  
  
  METHODS
  VSMC proliferation was determined by [(3)H]-thymidine incorporation, the uptake of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and cell number. Phosphorylated/non-phosphorylated IGF-1 receptor, Akt, mTOR and p70S6K expressions were determined by immunoblotting. The oligodeoxynucleotides were transfected to A10 cells to identify the effect of D1 and D5 receptors, respectively.
  
  
  RESULTS
  IGF-1 increased the proliferation of VSMCs, while in the presence of fenoldopam, IGF-1-mediated stimulatory effect was reduced. Use of either antisense for D1 or D5 receptor partially inhibited the fenoldopam-induced antiproliferation effect of VSMCs. Use of both D1 and D5 receptor antisenses completely blocked the inhibitory effect of fenoldopam. In the presence of PI3k and mTOR inhibitors, the IGF-1-mediated proliferation of VSMCs was blocked. Moreover, IGF-1 increased the phosphorylation of PI3k and mTOR. The inhibitory effect of fenoldopam on VSMC proliferation might be due to the inhibition of IGF-1 receptor expression and IGF-1 phosphorylation, because in the presence of fenoldopam, the stimulatory effect of IGF-1 on phosphorylation of IGF-1 receptor, PI3k and mTOR is reduced, the IGF-1 receptor expression was reduced in A10 cells.
  
  
  CONCLUSIONS
  Activation of the D1-like receptors suppressed the proliferative effect of IGF-1 in A10 cells via the inhibition of the IGF-1R/Akt/mTOR/p70S6K pathway and downregulated the expression of IGF-1 receptor.
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University , Chongqing , P.R. China and.
authors.forename: Xun
authors.initials: X
authors.lastname: Kou
authors.forename: Yu
authors.initials: Y
authors.lastname: Han
authors.forename: Di
authors.initials: D
authors.lastname: Yang
authors.forename: Yukai
authors.initials: Y
authors.lastname: Liu
authors.forename: Jinjuan
authors.initials: J
authors.lastname: Fu
authors.forename: Shuo
authors.initials: S
authors.lastname: Zheng
authors.forename: Duofen
authors.initials: D
authors.lastname: He
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.forename: Chunyu
authors.initials: C
authors.lastname: Zeng
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017447:Receptors, Dopamine D1 / Q000378:metabolism*
chemical_list: D017447:Receptors, Dopamine D1; C100987:dopamine D1C receptor; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases