title: Inhibitory effect of the D(3) dopamine receptor on insulin receptor expression and function in vascular smooth muscle cells.
abstract: BACKGROUND
  Vascular smooth muscle cell (VSMC) proliferation is regulated by numerous hormones and humoral factors. Our previous study found that stimulation of D(1)-like dopamine receptors inhibited insulin receptor expression and function in VSMCs. We hypothesize that there is also an interaction between D(3) dopamine and insulin receptors, i.e., stimulation of the D(3) receptor inhibits insulin receptor expression and function.
  
  
  METHODS
  Receptor expression was determined by immunoblotting, immunohistochemisty, and reverse transcriptase-PCR; VSMC proliferation was determined by 3-(4,5-dimethylthiazol-2-yl)-diphenyl-tetrazolium bromide (MTT) assay and cell number.
  
  
  RESULTS
  Insulin receptor protein is increased in the aorta of D(3) receptor deficient mice. Stimulation of the D(3) receptor inhibited insulin receptor mRNA and protein expression and insulin-mediated VSMC proliferation, and increased protein kinase A (PKA) activity, insulin receptor phosphorylation, and degradation in immortalized aortic VSMCs (A10 cells). These effects were blocked by a PKA inhibitor, indicating that the D(3) receptor-mediated decrease in insulin receptor expression was related to a decrease in transcription/post-transcription and increased degradation, involving PKA signaling.
  
  
  CONCLUSIONS
  D(3) receptor stimulation may be a target to reduce the adverse effect of insulin in hypertension by inhibition of insulin receptor expression and function in arterial VSMCs.
authors.affiliation: Department of Cardiology, Daping Hospital, The Third Military Medical University, Chongqing, People's Republic of China.
authors.forename: Hefei
authors.initials: H
authors.lastname: Huang
authors.forename: Yu
authors.initials: Y
authors.lastname: Han
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Wang
authors.forename: Caiyu
authors.initials: C
authors.lastname: Chen
authors.forename: Changqing
authors.initials: C
authors.lastname: Yu
authors.forename: Duofen
authors.initials: D
authors.lastname: He
authors.forename: Hongyong
authors.initials: H
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.forename: Laureano D
authors.initials: LD
authors.lastname: Asico
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Jose
authors.forename: Chunyu
authors.initials: C
authors.lastname: Zeng
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D001578:Benzopyrans / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D005260:Female; D008297:Male; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D010078:Oxazines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011972:Receptor, Insulin / Q000096:biosynthesis* / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000172:deficiency* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D001578:Benzopyrans; D010078:Oxazines; D012333:RNA, Messenger; D050637:Receptors, Dopamine D3; C062458:3,4,4a,10b-tetrahydro-4-propyl-2H,5H-(1)benzopyrano(4,3-b)-1,4-oxazin-9-ol; D011972:Receptor, Insulin; D017868:Cyclic AMP-Dependent Protein Kinases