title: Morphine-induced postconditioning modulates mitochondrial permeability transition pore opening via delta-1 opioid receptors activation in isolated rat hearts.
abstract: BACKGROUND
  It is generally accepted that morphine affords cardioprotection against ischemia/reperfusion injury. Inhibition of the mitochondrial permeability transition pore (MPTP) is considered an end target for cardioprotection. The aim of this study was to investigate the involvement of opioid receptors (OR) and MPTP in morphine-induced postconditioning (M-Post).
  
  
  METHODS
  Isolated rat hearts were subjected to 30 min of regional ischemia and 2 h of reperfusion. Hearts were treated with 1 µM morphine, with or without the OR antagonists or a MPTP opener at early reperfusion. Infarct size was measured with 2,3,5-triphenyltetrazolium chloride staining.
  
  
  RESULTS
  There were no significant differences in cardiodynamic variables except a decrease in heart rate in the M-Post group (P < 0.01 vs. control) after reperfusion. M-Post dramatically reduced infarct-risk volume ratio (9.8 ± 2.5%, P < 0.001 vs. 30.0 ± 3.7% in control). This beneficial effect on infarct volume by M-Post was comparable with ischemic postconditioning (11.9 ± 2.2%, P > 0.05). The nonspecific OR antagonist naloxone (25.7 ± 1.9%, P < 0.01), the δ-OR antagonist naltrindole (27.8 ± 4.3%, P < 0.05) and δ(1)-OR antagonist 7-benzylidenenaltrexone (24.7 ± 3.7%, P < 0.01) totally abrogated the anti-infarct effect of M-Post. In addition, the anti-infarct effect by M-Post was also totally blocked by the MPTP opener atractyloside (26.3 ± 5.2%, P < 0.05).
  
  
  CONCLUSIONS
  M-Post effectively reduces myocardial infarction. The anti-infarct effect by M-Post is mediated via activation of δ-OR, especially δ(1)-OR, and inhibition of the MPTP opening.
authors.affiliation: Institute of Cardiovascular Research, Pusan National University Yangsan Hospital, Yangsan, Korea.
authors.forename: June Hong
authors.initials: JH
authors.lastname: Kim
authors.forename: Kook Jin
authors.initials: KJ
authors.lastname: Chun
authors.forename: Yong Hyun
authors.initials: YH
authors.lastname: Park
authors.forename: Jun
authors.initials: J
authors.lastname: Kim
authors.forename: Jeong Su
authors.initials: JS
authors.lastname: Kim
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Jang
authors.forename: Mi Young
authors.initials: MY
authors.lastname: Lee
authors.forename: Jae Hong
authors.initials: JH
authors.lastname: Park