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

  • Membranes (Basel). 2023 Jan 4;13(1):63. doi: 10.3390/membranes13010063.
Sergey V Popov  1 ,  Alexandr V Mukhomedzyanov  1 ,  Leonid N Maslov  1 ,  Natalia V Naryzhnaya  1 ,  Boris K Kurbatov  1 ,  N Rajendra Prasad  2 ,  Nirmal Singh  3 ,  Feng Fu  4 ,  Viacheslav N Azev  5
Affiliations
  • 1. Laboratory of Experimental Cardiology, Cardiology Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences, 634012 Tomsk, Russia.
  • 2. Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Chidambaram 608002, India.
  • 3. Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, India.
  • 4. Department of Physiology and Pathophysiology, Fourth Military Medical University, Xi'an 710032, China.
  • 5. The Branch of the Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997 Pushchino, Russia.
PMID: 36676870 DOI: 10.3390/membranes13010063
Abstract

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.

Keywords
KATP channels; heart; ischemia; kinases; opioid receptors; reperfusion.
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