Opioid receptor contributes to ischemic preconditioning through protein kinase C activation in rabbits.
Recent studies have reported that protection from ischemic preconditioning (PC) is blocked by the opioid receptor antagonist naloxone (NAL). We tested whether an opioid agonist could mimic PC in the rabbit heart, whether that protection involved protein kinase C (PKC) activation, and whether opioid receptors act in concert with other PKC-coupled receptors. Rabbit hearts were subjected to 30 min coronary occlusions and were reperfused for either 3 (in situ) or 2 (in vitro) h. Infarct size was determined by staining with triphenyltetrazolium chloride. In untreated in situ hearts 38.5+/-1.6% of the risk zone infarcted. PC with 5 min ischemia/10 min reperfusion significantly limited infarction to 12.7+/-2.9% (p < 0.01). NAL infusion did not modify infarction (39.6+/-1.6%) in non-PC hearts, but blocked the effect of one cycle of PC (34.4+/-3.6% infarction). NAL, however, could not block cardioprotection when PC was amplified with 3 cycles of ischemia/reperfusion (9.9+/-1.4% infarction, p < 0.01 vs. control). Morphine could also mimic ischemic preconditioning, but only at a dose much higher than would be used clinically (3 mg/kg). In isolated hearts pretreatment with morphine (0.3 microM) significantly limited infarction to 9.3+/-1.2% (p < 0.01 vs. 32.0+/-3.1% in controls). This cardioprotective effect of morphine could be blocked by either the PKC inhibitor chelerythrine (30.4+/-2.6% infarction) or NAL (34.0+/-2.6% infarction). Neither chelerythrine nor NAL by itself modified infarction in non-PC hearts. NAL could not block protection from one cycle of PC in isolated hearts indicating that an intact innervation may be required for endogenous opioid production. Thus, opioid receptors, like other PKC-coupled receptors, participate in the triggering of PC in the rabbit heart.
Miki
T
T
Department of Physiology, University of South Alabama, College of Medicine, Mobile 36688, USA.
Cohen
M V
MV
Downey
J M
JM
D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009203:Myocardial Infarction / Q000378:metabolism / Q000517:prevention & control; D017202:Myocardial Ischemia / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000517:prevention & control; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D010617:Phenanthridines / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D011817:Rabbits; D011957:Receptors, Opioid / Q000378:metabolism*
D000470:Alkaloids; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D009292:Narcotic Antagonists; D010617:Phenanthridines; D011957:Receptors, Opioid; D009270:Naloxone; D009020:Morphine; C016299:chelerythrine; D011493:Protein Kinase C