Delta opioid receptor stimulation mimics ischemic preconditioning in human heart muscle.
OBJECTIVE
The objective of this study was to examine whether the delta (delta) opioid receptor isoform is expressed in the human heart and whether this receptor improves contractile function after hypoxic/reoxygenation injury.


BACKGROUND
Delta opioid receptor agonists mimic preconditioning (PC) in rat myocardium, corresponding to known cardiac delta opioid receptor expression in this species.


METHODS
The messenger RNA transcript encoding the delta opioid receptor was identified in human atria and ventricles. To evaluate the cardioprotective role of the opioid receptor, human atrial trabeculae from patients undergoing coronary bypass grafting were isolated and superfused with Tyrode's solution. A control group underwent 90 min of simulated ischemia and 120 min of reoxygenation. A second group was preconditioned with 3 min simulated ischemia and 7 min reoxygenation. Additional groups included: superfusion with the delta receptor agonist (DADLE) (10 nM), with the delta receptor antagonist naltrindole (10 nM) and with the mitochondrial K(ATP) channel blocker 5-hydroxydecanoate (5HD) (100 microM) either with or without PC, respectively. A final group was superfused with 5HD before DADLE. The end point used was percentage of developed force after 120 min of reoxygenation.


RESULTS
Results, expressed as means +/- SEM, were: control = 32.6 + 3.8%; PC = 50.5% + 1.8*; DADLE = 46.0+/-3.9%*; PC + naltrindole = 25.5+/-3.9%; naltrindole alone = 25.5+/-4.3%; 5HD + PC = 28.9+/-7.4%; 5HD alone = 24.1+/-3.0%; 5HD + DADLE = 26.9+/-4.4% (*p < 0.001 vs. controls).


CONCLUSIONS
Human myocardium expresses the delta opioid receptor transcript. Stimulation of this receptor appears to protects human muscle from simulated ischemia, similar to PC, and via opening of the mitochondrial K(ATP) channel.
Bell
S P
SP
The Hatter Institute, University College London Hospitals and Medical School, United Kingdom.
Sack
M N
MN
Patel
A
A
Opie
L H
LH
Yellon
D M
DM
D006801:Humans; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D015221:Potassium Channels / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D017465:Receptors, Opioid, delta / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D015221:Potassium Channels; D012333:RNA, Messenger; D017465:Receptors, Opioid, delta