Activation of peripheral δ₂-opioid receptor prevents reperfusion heart injury

Coronary artery occlusion (45 min) and reperfusion (2 h) was performed in rats anesthetized with α-chloralose. Opioid receptor agonists were administered intravenously 5 min before reperfusion, while opioid receptor antagonists were administered 10 min before reperfusion. The non-selective opioid δ-receptor agonist DADLE at a dose of 0.088 mg/kg had no effect the infarct size/area at risk ratio. The selective opioid δ-receptor agonist BW373 was administered at a dose of 1 mg/kg. This opioid at a dose of 1 mg/kg reduced infarct size. The selective opioid δ₁-receptor agonist DPDPE at a dose of 0.1 mg/kg and 0.969 mg/kg did not affect infarct size. The selective opioid δ₂-receptor agonist deltorphin II at a dose of 0.12 mg/kg reduced infarct size by one half. The opioid δ-receptor agonist p-Cl-Phe-DPDPE was administered at a dose of 0.105 mg/kg and 1.02 mg/kg. This opioid at a dose of 1.02 mg/kg reduced infarct size. The universal opioid receptor antagonists, naltrexone and naloxone methiodide acting on peripheral opioid receptor, as well as the selective opioid δ-receptor antagonist TIIP[ψ], the selective opioid δ₂-receptor antagonist naltriben eliminated the infarct limiting effect of deltorphin II. The selective opioid κ receptor antagonist nor-binaltorphimine, the selective opioid μ receptor antagonist CTAP, and the selective opioid δ₁-receptor antagonist BNTX did not abolish the protective effect of deltorphin II. Deltorphin II exhibited the most pronounced cardioprotective effect during reperfusion. These studies clearly indicate that the activation of opioid δ₂-receptor located in cardiomyocytes increases the resistance of the heart to reperfusion injury.