title: Kappa-opioid receptor activation during reperfusion limits myocardial infarction via ERK1/2 activation in isolated rat hearts.
abstract: BACKGROUND
  We investigated whether p42/p44 extracellular signal-regulated kinases (ERK1/2) and/or phosphatidylinositol-3-OH kinase (PI3K)-Akt play a crucial role in cardioprotection by κ-opioid receptor (KOP) activation.
  
  
  METHODS
  Langendorff perfused rat hearts were subjected to 30 min of regional ischemia and 2 h of reperfusion. Antagonists of ERK1/2 and PI3K were perfused in hearts treated with the KOP agonist U50488H (U50). Infarct size was measured after 2 h of reperfusion. The phosphorylation states of ERK1/2 and Akt by Western immunoblots were determined. Drugs were perfused for a period of 5 min before and 30 min after reperfusion.
  
  
  RESULTS
  Inhibition of ERK1/2 (26.8 ± 2.9%, P < 0.05 vs. U50) but not PI3K (15.5 ± 1.1%, P > 0.05 vs. U50) completely abrogated the anti-infarct effect of U50488H. Western blot analysis revealed a significant increase in ERK1/2 but not Akt phsophorylation in U50488H-treated hearts as compared to control hearts when measured immediately after reperfusion.
  
  
  CONCLUSIONS
  KOP activation effectively reduces myocardial infarction. The anti-infarct effect of U50488H is mediated by the ERK1/2, but not the PI3K-Akt pathway.
authors.affiliation: Institute of Cardiovascular Research Center, Pusan National University Yangsan Hospital, Yangsan, Korea.
authors.forename: June Hong
authors.initials: JH
authors.lastname: Kim
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Jang
authors.forename: Kook Jin
authors.initials: KJ
authors.lastname: Chun
authors.forename: Jun
authors.initials: J
authors.lastname: Kim
authors.forename: Yong Hyun
authors.initials: YH
authors.lastname: Park
authors.forename: Jeong Su
authors.initials: JS
authors.lastname: Kim
authors.forename: Jin Mo
authors.initials: JM
authors.lastname: Kim
authors.forename: Mi Young
authors.initials: MY
authors.lastname: Lee