Activation of peripheral δ2-opioid receptor prevents reperfusion heart injury

Leonid Maslov*, Alexander Mukhomedzyanov, Sergey Tsibulnikov, M-Saadeh Suleiman, Igor Khaliulin, Peter R. Oeltgen

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

Abstract

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.
Original languageEnglish
Article number174302
Number of pages6
JournalEuropean Journal of Pharmacology
Volume907
Early online date1 Jul 2021
Publication statusPublished - 15 Sep 2021

Keywords

  • heart
  • reperfusion
  • opoids
  • Opioid δ-receptor

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