Activation of peripheral δ2-opioid receptor prevents reperfusion heart injury

Маслов, Л Н; Mukhomedzyanov, A. V.; Tsibulnikov, S. Yu.; Suleiman, M‐Saadeh; Khaliulin, Igor; Oeltgen, Peter R.

doi:10.1016/j.ejphar.2021.174302

Cited by 13 publications

(20 citation statements)

References 21 publications

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“…It was shown that the infarct-reducing effect of deltorphin II is mediated via the activation of peripheral δ 2 OR. These data are consistent with our previously published data [ 4 ]. This δ 2 OR appears to be localized on the sarcolemma of cardiomyocytes, because deltorphin II increases the resistance of isolated cardiomyocytes to anoxia/reoxygenation via the stimulation of δ 2 OR [ 4 ].…”

Section: Discussionsupporting

confidence: 94%

“…The selective δ 2 OR agonist deltorphin II was administered intravenously 5 min prior to reperfusion at a dose of 0.12 mg/kg [ 5 ]. The choice of the doses of OR antagonists and the administration schedule were based on our previously published data [ 4 , 5 ]. Naltrexone, which is an antagonist of all types of OR, was used at a dose of 5 mg/kg [ 5 ].…”

Section: Methodsmentioning

confidence: 99%

“…The results of our preliminary studies indicated that OR agonists can prevent not only ischemic, but also reperfusion injury of the heart [ 4 ]. There are potential reasons to believe that OR agonists can serve as a prototype for creating a new class of drugs that increase cardiac resistance to reperfusion.…”

Section: Introductionmentioning

confidence: 99%

“…In 2009, we found that the selective δ 2 OR agonist deltorphin II could prevent cardiac I/R injury when administered before ischemia [ 5 ]. In 2021, we found that deltorphin II can prevent reperfusion injury of the heart [ 4 ]. Our studies indicated that the infarct-reducing effect of deltorphin II is mediated via the activation of δ 2 OR in cardiomyocytes [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…In 2021, we found that deltorphin II can prevent reperfusion injury of the heart [ 4 ]. Our studies indicated that the infarct-reducing effect of deltorphin II is mediated via the activation of δ 2 OR in cardiomyocytes [ 4 ]. However, the molecular mechanism of the cardioprotective effect of deltorphin II in reperfusion remains unknown.…”

Section: Introductionmentioning

confidence: 99%

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The Infarct-Reducing Effect of the δ2 Opioid Receptor Agonist Deltorphin II: The Molecular Mechanism

et al. 2023

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The search for novel drugs for the treatment of acute myocardial infarction and reperfusion injury of the heart is an urgent aim of modern pharmacology. Opioid peptides could be such potential drugs in this area. However, the molecular mechanism of the infarct-limiting effect of opioids in reperfusion remains unexplored. The objective of this research was to study the signaling mechanisms of the cardioprotective effect of deltorphin II in reperfusion. Rats were subjected to coronary artery occlusion (45 min) and reperfusion (2 h). The ratio of infarct size/area at risk was determined. This study indicated that the cardioprotective effect of deltorphin II in reperfusion is mediated via the activation of peripheral δ2 opioid receptor (OR), which is most likely localized in cardiomyocytes. We studied the role of guanylyl cyclase, protein kinase Cδ (PKCδ), phosphatidylinositol-3-kinase (PI3-kinase), extracellular signal-regulated kinase-1/2 (ERK1/2-kinase), ATP-sensitive K+-channels (KATP channels), mitochondrial permeability transition pore (MPTP), NO synthase (NOS), protein kinase A (PKA), Janus 2 kinase, AMP-activated protein kinase (AMPK), the large conductance calcium-activated potassium channel (BKCa-channel), reactive oxygen species (ROS) in the cardioprotective effect of deltorphin II. The infarct-reducing effect of deltorphin II appeared to be mediated via the activation of PKCδ, PI3-kinase, ERK1/2-kinase, sarcolemmal KATP channel opening, and MPTP closing.

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Section: Discussionsupporting

confidence: 94%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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