Signaling mechanisms of the cardioprotective effect of peptide and nonpeptide opioid receptor agonists in cardiac reperfusion (literature review)

In-hospital mortality in patients with acute myocardial infarction (AMI) is 5% 8% and has not decreased in recent years. One of the reasons for high mortality is reperfusion cardiac injury. It is quite obvious that there is an urgent need to develop drugs that can effectively reduce mortality in AMI. Opioids could become such drugs. The activation of peripheral µ2-, δ2-, κ1-opioid receptors (ORs) reduces the size of the infarction and improves contractility in reperfusion. Peripheral µ1-, δ1-, κ2ORs is not involved in the regulation of cardiac tolerance to reperfusion injury. PI3-kinase (phosphoinositide 3-kinase), ERK1/2 (extracellular signal-regulated kinase-1/2), Akt-kinase, epidermal growth factor receptor (EGRF) and soluble guanylyl cyclase (sGC) are involved in the cardioprotective effect of opioid postconditioning. Inhibition of GSK-3β (glycogen synthase kinase3β) and JNK (c-jun NH2 amino-terminal kinase) is involved in opioid postconditioning in contrast to Janus kinase-2 (JAK2) and protein kinase A (PKA). There is evidence that hemeoxygenase-1 (HO-1) and NO synthase (NOS) are also involved in opioidinduced postconditioning. Peptide and non-peptide µ2-, δ2-, κ1-OR agonists may become drugs for the treatment of AMI. Aim is to analyze signaling mechanisms of the cardioprotective effect of peptide and non-peptide opioid receptor agonists during cardiac reperfusion. A literature search was carried out in the PubMed database with queries “opioid receptors”, “opioid receptor agonists”, “cardioprotective effect of opioid receptor agonists”.

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