title: Increase of PPARδ by dopamine mediated via DA-1 receptor-linked phospholipase C pathway in neonatal rat cardiomyocytes.
abstract: BACKGROUND
  Role of peroxisome proliferator-activated receptor δ (PPARδ) in cardiac contraction has recently been established. Dopamine is one of the agents used to treat heart failure in clinics. But the mediation of PPARδ in cardiac action of dopamine is still unclear.
  
  
  METHODS
  The present study is aimed to clarify this point using neonatal rat cardiomyocytes to investigate the changes of PPARδ expression and cardiac troponin I (cTnI) phosphorylation by Western blotting analysis. Antagonists of receptors, inhibitor of phospholipase C (PLC) (U73122), calcium chelator (BAPTA-AM), and inhibitor of protein kinase A (PKAI) were also applied. We silenced PPARδ by RNAi to identify the major role of PPARδ in dopamine-induced actions.
  
  
  RESULTS
  Dopamine increases PPARδ expression and cardiac troponin I (cTnI) phosphorylation in a time- and dose-dependent manner in neonatal rat cardiomyocytes. Moreover, both actions of dopamine were blocked by DA1 receptor antagonist and PLC inhibitor but not by PKAI. The increase of cTnI phosphorylation by dopamine was also inhibited in cardiomyocytes silenced by RNAi of PPARδ.
  
  
  CONCLUSIONS
  We suggest that dopamine can enhance cardiac contraction mainly through an activation of DA1 receptor-linked PLC pathway to increase cellular calcium ions for the increase of PPARδ expression.
authors.affiliation: Department of Internal Medicine - Cardiology, Taipei City Hospital - Zhongxing Branch, Datong Dist., Taipei City 10341, Taiwan.
authors.forename: Shih-Hsiang
authors.initials: SH
authors.lastname: Lo
authors.forename: Kung-Shing
authors.initials: KS
authors.lastname: Lee
authors.forename: Li-Jen
authors.initials: LJ
authors.lastname: Chen
authors.forename: Juei-Tang
authors.initials: JT
authors.lastname: Cheng
authors.forename: Chih-Hsiung
authors.initials: CH
authors.lastname: Chen
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D004298:Dopamine / Q000494:pharmacology / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D047494:PPAR delta / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors; D047494:PPAR delta; D017447:Receptors, Dopamine D1; D010738:Type C Phospholipases; D004298:Dopamine
keywords: DA1 receptor; Dopamine; Neonatal cardiomyocytes; PPARδ; Phospholipase C