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Deltorphin‐II Mimics the Postconditioning Phenomenon: the Role of Opioid Receptors and the Signaling Mechanism
Author(s) -
Naryzhnaya Natalia,
Popov Sergey,
Tsibulnikov Sergey,
Mukhomedzyanov Alexander,
Kurbatov Boris,
Maslov Leonid
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.05116
Subject(s) - pharmacology , myocardial infarction , agonist , receptor , chemistry , protein kinase c , reperfusion injury , medicine , opioid , signal transduction , ischemia , biochemistry
The development of new drugs for treatment of acute myocardial infarction is an urgent aim of modern pharmacology. Opioid peptides can serve as the basis for the creation of such drugs. We hypothesized that deltorphin‐II can mimic postconditioning of the heart. The aim of this research is to study the receptor and signaling mechanisms of the cardioprotective effect of deltorphin‐II at reperfusion. Rats were subjected to coronary artery occlusion (45 min) and reperfusion (2 h). It was assessed the infarct size/area at risk ratio. The selective δ 2 opioid receptor (OR) agonist deltorphin‐II was injected intravenously 5 min before reperfusion. OR antagonists, inhibitors of kinases and inhibitors of other molecular structures were administered 10 min before reperfusion. It was established that the cardioprotective effect of deltorphin‐II at reperfusion is mediated via the activation of peripheral δ 2 OR which is probably localized in cardiomyocytes. The infarct‐reducing effect of deltorphin‐II is mediated via the activation of guanylyl cyclase, PKCδ, PI3 kinase, ERK1/2, sarcK ATP channel opening, MPT pore closing. These data indicate that δ 2 OR agonists may be used for prevention of reperfusion cardiac injury.