title: Function and expression differences between ergot and non-ergot dopamine D2 agonists on heart valve interstitial cells.
abstract: OBJECTIVE
  The symptoms of Parkinson's disease are alleviated by dopamine D2 agonists, which are classified as ergot dopamine D2 agonists and non-ergot D2 agonists. Among the former, pergolide has been associated with valvular heart disease, since it has both potent D2 receptor and serotonin 5-HT(2B) receptor agonistic properties. Among the latter, pramipexole has few incidences of heart valve disease onset, since it has an absence of 5-HT(2B) receptor agonism.
  
  
  METHODS
  A [3H]thymidine incorporation assay was performed to monitor function, and microarray global analysis to monitor gene expression, on porcine heart valve interstitial cells (VICs) treated with pergolide or pramipexole.
  
  
  RESULTS
  The 5-HT(2B) receptor was abundantly expressed in porcine VICs. The 5-HT(2B) receptor agonist pergolide induced an increase in [3H]thymidine incorporation, accompanied by a decrease in 5-HT(2B) receptor mRNA expression. [3H]thymidine incorporation was blocked by lisuride, a 5-HT(2B) receptor antagonist, and also by LY-294002, a specific inhibitor of PI3K and Akt. Moreover, type 2 iodothyronine deiodinase (Dio2) expression in porcine VICs treated with pergolide was shown, by a global analysis of mRNA, to be markedly increased compared to that induced by pramipexole. Such changes in VICs may correlate with the mechanism of heart valve disease pathogenesis.
  
  
  CONCLUSIONS
  There were substantial differences (increased [3H]thymidine incorporation, and Dio2 expression) between pergolide and pramipexole, which might correlate with the mechanism of heart valve disease onset.
authors: Fumiki
authors: F
authors: Oana
authors: Hiroshi
authors: H
authors: Onozuka
authors: Akihiro
authors: A
authors: Tsuchioka
authors: Takayuki
authors: T
authors: Suzuki
authors: Nobuyuki
authors: N
authors: Tanaka
authors: Kouichi
authors: K
authors: Kaidoh
authors: Yuji
authors: Y
authors: Hoyano
authors: Masahiro
authors: M
authors: Hiratochi
authors: Shinji
authors: S
authors: Kikuchi
authors: Yasuo
authors: Y
authors: Takehana
authors: Nobuo
authors: N
authors: Shibata
mesh_terms: D000818:Animals; D052160:Benzothiazoles / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018491:Dopamine Agonists / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D008943:Mitral Valve / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010479:Pergolide / Q000633:toxicity*; D000077487:Pramipexole; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D044403:Receptor, Serotonin, 5-HT2B / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000378:metabolism; D015203:Reproducibility of Results; D058826:Serotonin 5-HT2 Receptor Agonists / Q000633:toxicity; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D052160:Benzothiazoles; D018491:Dopamine Agonists; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D044403:Receptor, Serotonin, 5-HT2B; D017448:Receptors, Dopamine D2; D058826:Serotonin 5-HT2 Receptor Agonists; D058830:Serotonin 5-HT2 Receptor Antagonists; D010479:Pergolide; D000077487:Pramipexole