title: Role of dopamine D2 receptors in ischemia/reperfusion induced apoptosis of cultured neonatal rat cardiomyocytes.
abstract: BACKGROUND
  Myocardial ischemia/reperfusion injury is the major cause of morbidity and mortality for cardiovascular diseases. Dopamine D2 receptors are expressed in cardiac tissues. However, the roles of dopamine D2 receptors in myocardial ischemia/reperfusion injury and cardiomyocyte apoptosis are unclear. Here we investigated the effects of both dopamine D2 receptors agonist (bromocriptine) and antagonist (haloperidol) on apoptosis of cultured neonatal rat ventricular myocytes induced by ischemia/reperfusion injury.
  
  
  METHODS
  Myocardial ischemia/reperfusion injury was simulated by incubating primarily cultured neonatal rat cardiomyocytes in ischemic (hypoxic) buffer solution for 2 h. Thereafter, these cells were incubated for 24 h in normal culture medium.
  
  
  RESULTS
  Treatment of the cardiomyocytes with 10 μM bromocriptine significantly decreased lactate dehydrogenase activity, increased superoxide dismutase activity, and decreased malondialdehyde content in the culture medium. Bromocriptine significantly inhibited the release of cytochrome c, accumulation of [Ca2+]i, and apoptosis induced by ischemia/reperfusion injury. Bromocriptine also down-regulated the expression of caspase-3 and -9, Fas and Fas ligand, and up-regulated Bcl-2 expression. In contrast, haloperidol (10 μM) had no significant effects on the apoptosis of cultured cardiomyocytes under the aforementioned conditions.
  
  
  CONCLUSIONS
  These data suggest that activation of dopamine D2 receptors can inhibit apoptosis of cardiomyocytes encountered during ischemia/reperfusion damage through various pathways.
authors.affiliation: Department of Pathophysiology, Harbin Medical University, Harbin, PR China.
authors.forename: Hong-zhu
authors.initials: HZ
authors.lastname: Li
authors.forename: Jin
authors.initials: J
authors.lastname: Guo
authors.forename: Jun
authors.initials: J
authors.lastname: Gao
authors.forename: Li-ping
authors.initials: LP
authors.lastname: Han
authors.forename: Chun-ming
authors.initials: CM
authors.lastname: Jiang
authors.forename: Hong-xia
authors.initials: HX
authors.lastname: Li
authors.forename: Shu-zhi
authors.initials: SZ
authors.lastname: Bai
authors.forename: Wei-hua
authors.initials: WH
authors.lastname: Zhang
authors.forename: Guang-wei
authors.initials: GW
authors.lastname: Li
authors.forename: Li-na
authors.initials: LN
authors.lastname: Wang
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: Ya-jun
authors.initials: YJ
authors.lastname: Zhao
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.forename: Guang-dong
authors.initials: GD
authors.lastname: Yang
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Ling-yun
authors.initials: LY
authors.lastname: Wu
authors.forename: Bao-feng
authors.initials: BF
authors.lastname: Yang
authors.forename: Chang-qing
authors.initials: CQ
authors.lastname: Xu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001971:Bromocriptine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D065127:Dopamine D2 Receptor Antagonists; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism*
chemical_list: D065127:Dopamine D2 Receptor Antagonists; D017448:Receptors, Dopamine D2; D001971:Bromocriptine; D006220:Haloperidol; D002118:Calcium