title: Morphine induces preconditioning via activation of mitochondrial K(Ca) channels.
abstract: OBJECTIVE
  Mitochondrial calcium sensitive potassium (mK(Ca)) channels are involved in cardioprotection induced by ischemic preconditioning. In the present study we investigated whether morphine-induced preconditioning also involves activation of mK(Ca) channels.
  
  
  METHODS
  Isolated rat hearts (six groups; each n = 8) underwent global ischemia for 30 min followed by a 60-min reperfusion. Control animals were not further treated. Morphine preconditioning (MPC) was initiated by two five-minute cycles of morphine 1 microM infusion with one five-minute washout and one final ten-minute washout period before ischemia. The mK(Ca) blocker, paxilline 1 microM, was administered, with and without morphine administration (MPC + Pax and Pax). As a positive control, we added an ischemic preconditioning group (IPC) alone and combined with paxilline (IPC + Pax). At the end of reperfusion, infarct sizes were determined by triphenyltetrazoliumchloride staining.
  
  
  RESULTS
  Infarct size was (mean +/- SD) 45 +/- 9% of the area at risk in the Control group. The infarct size was less in the morphine or ischemic preconditioning groups (MPC: 23 +/- 8%, IPC: 20 +/- 5%; each P < 0.05 vs Control). Infarct size reduction was abolished by paxilline (MPC + Pax: 37 +/- 7%, P < 0.05 vs MPC and IPC + Pax: 36 +/- 6%, P < 0.05 vs IPC), whereas paxilline alone had no effect (Pax: 46 +/- 7%, not significantly different from Control).
  
  
  CONCLUSIONS
  Cardioprotection by morphine-induced preconditioning is mediated by activation of mK(Ca) channels.
authors.affiliation: Department of Anesthesiology, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Frässdorf
authors.forename: Ragnar
authors.initials: R
authors.lastname: Huhn
authors.forename: Corinna
authors.initials: C
authors.lastname: Niersmann
authors.forename: Nina C
authors.initials: NC
authors.lastname: Weber
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Schlack
authors.forename: Benedikt
authors.initials: B
authors.lastname: Preckel
authors.forename: Markus W
authors.initials: MW
authors.lastname: Hollmann
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001835:Body Weight; D006439:Hemodynamics / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009020:Morphine / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D009929:Organ Size; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000819:agonists* / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000701:Analgesics, Opioid; D007211:Indoles; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; C048220:paxilline; D009020:Morphine
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