Morphine induces preconditioning via activation of mitochondrial K(Ca) channels.
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.
Frässdorf
Jan
J
Department of Anesthesiology, Academic Medical Center, University of Amsterdam, The Netherlands.
Huhn
Ragnar
R
Niersmann
Corinna
C
Weber
Nina C
NC
Schlack
Wolfgang
W
Preckel
Benedikt
B
Hollmann
Markus W
MW
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
D000701:Analgesics, Opioid; D007211:Indoles; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; C048220:paxilline; D009020:Morphine
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