GSK3β inhibition and KATP channel opening mediate acute opioid-induced cardioprotection at reperfusion

  title={GSK3$\beta$ inhibition and KATP channel opening mediate acute opioid-induced cardioprotection at reperfusion},
  author={Eric R. Gross and Anna K. Hsu and Garrett John Gross},
  journal={Basic Research in Cardiology},
Both glycogen synthase kinase 3β (GSK3β) and the ATP-dependant potassium channel (KATP) mediate opioid-induced cardioprotection (OIC). However, whether direct KATP channel openers induce cardioprotection prior to reperfusion and their signaling cascade position with respect to GSK3β inhibition is unknown. Therefore, we investigated the role of KATP channel opening at reperfusion in OIC, and the interaction between the GSK signaling axis and KATP channels in cardioprotection.Male Sprague-Dawley… 
Morphine-induced postconditioning modulates mitochondrial permeability transition pore opening via delta-1 opioid receptors activation in isolated rat hearts
M-Post effectively reduces myocardial infarction and the anti-infarct effect by M-Post is mediated via activation of δ-OR, especially δ1- OR, and inhibition of the MPTP opening.
Activation of kappa-opioid receptors at reperfusion affords cardioprotection in both rat and mouse hearts
It is shown that κ-ORs afford cardioprotection primarily when activated prior to and not after reperfusion, and this protection may involve activation of the PI3 kinase (PI3K) pathway and mitochondrial (mito) KATP channels.
Morphine and remifentanil-induced cardioprotection: its experimental and clinical outcomes
This review will discuss OIC using mostly morphine and remifentanil which are widely used during cardiac anesthesia in addition to the clinical implications of OIC.
Morphine Reduces Myocardial Infarct Size via Heat Shock Protein 90 in Rodents
Data suggest that opioid-induced cardioprotection is mediated by HSP90, and part of this protection afforded by H SP90 is downstream of GSK3β, potentially via the HSP-TOM mitochondrial import pathway.
Cardioprotective PKG-independent NO signaling at reperfusion.
Protection from PKG activator 8-(4-chlorophenylthio)-guanosine 3',5'-cyclic monophosphate (CPT-cGMP) at reperfusion was found, suggesting a PKG-independent NO synthase in IPC's mediator pathway downstream of PKG and A(2b)AR and its protection is independent ofPKG.
ROS-Independent Preconditioning in Neurons via Activation of mitoKATP Channels by BMS-191095
  • T. Gáspár, J. Snipes, D. Busija
  • Biology
    Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
  • 2008
Key components of the cascade resulting in delayed neuronal PC with BMS are identified using isolated rat brain mitochondria and primary cultures of rat cortical neurons and catalase inhibitor 3-aminotriazole dose-dependently antagonized the neuroprotective effect of BMS.
Inhibition of Phosphodiesterases Leads to Prevention of the Mitochondrial Permeability Transition Pore Opening and Reperfusion Injury in Cardiac H9c2 Cells
Inhibition of PDEs prevents the mPTP opening by inactivating GSK-3β through PKA and PKG and may be a useful approach to prevent reperfusion injury.
Postconditioning Prevents Reperfusion Injury by Activating &dgr;-Opioid Receptors
Nitric oxide–cyclic guanosine monophosphate–protein kinase G pathway may account for the effect of postconditioning on the mPTP opening, and morphine produces nitric oxide in cardiomyocytes by activating opioid receptors.
Role of Opioid Receptors Signaling in Remote Electrostimulation - Induced Protection against Ischemia/Reperfusion Injury in Rat Hearts
The mechanism of RES-induced myocardial protection against I/R injury seems to involve multiple target pathways such as Akt, KOR and/or DOR signaling.
The effect of butorphanol postconditioning on myocardial ischaemia reperfusion injury in rats.
The results suggest that postconditioning of butorphanol tartrate can provide a potent cardioprotective effect against myocardial ischaemic and reperfusion injury in rats.


Opioid-Induced Cardioprotection Occurs via Glycogen Synthase Kinase β Inhibition During Reperfusion in Intact Rat Hearts
Data indicate that OIC occurs via the phosphorylation of GSKβ at Ser9 in the ischemic zone during reperfusion through phosphatidylinositol-3 kinase through PI3K and target of rapamycin.
TAN-67, a δ1-opioid receptor agonist, reduces infarct size via activation of Gi/o proteins and KATP channels.
These results are the first to suggest that stimulating the δ1-opioid receptor elicits a cardioprotective effect that is mediated via Gi/o proteins and KATP channels in the intact rat heart.
TAN-67, a delta 1-opioid receptor agonist, reduces infarct size via activation of Gi/o proteins and KATP channels.
These results are the first to suggest that stimulating the delta 1-opioid receptor elicits a cardioprotective effect that is mediated via Gi/o proteins and KATP channels in the intact rat heart.
K(ATP) opener-induced delayed cardioprotection: involvement of sarcolemmal and mitochondrial K(ATP) channels, free radicals and MEK1/2.
Opioid-induced cardioprotection against myocardial infarction and arrhythmias: mitochondrial versus sarcolemmal ATP-sensitive potassium channels.
The data suggest that delta(1)-opioid receptor stimulation is cardioprotective against myocardial ischemia and sublethal arrhythmias and suggest a role for the mitochondrial K(ATP) channel in mediating these cardioprotsective effects.
Cytochrome P450 omega-hydroxylase inhibition reduces infarct size during reperfusion via the sarcolemmal KATP channel.
Protection of cardiac myocytes via δ1-opioid receptors, protein kinase C, and mitochondrial KATP channels
The results suggest that the delta(1)-opioid receptor is present on cardiac myocytes and mediates a potent cardioprotective effect via protein kinase C and the mitochondrial K(ATP) channel.
The effects of ischaemic preconditioning, diazoxide and 5‐hydroxydecanoate on rat heart mitochondrial volume and respiration
In isolated mitochondria, 5HD was rapidly converted to 5HD‐CoA by mitochondrial fatty acyl CoA synthetase and acted as a weak substrate or inhibitor of respiration depending on the conditions employed and highlighted the dangers of using 5HD and diazoxide as specific modulators of mitoKATP channels in the heart.
Direct preconditioning of cardiac myocytes via opioid receptors and KATP channels.
Results provide direct evidence that the preconditioning-like effect of morphine in the intact heart can be exerted at the level of cardiac myocytes and is most likely the result of mitochondrial KATP channel activation.
Cardiomyocyte mitochondrial KATP channels participate in the antiarrhythmic and antiinfarct effects of KATP activators during ischemia and reperfusion in an intact anesthetized rabbit model.
Higher levels of malondialdehyde and lower levels of reduced glutathione and superoxide dismutase in necrotic zone of myocardium in all subgroups in Group II suggest little anti-free radical property of NIC and PIN, and it may be assumed that mitochondrial K(ATP) channel opening leads to mitochondrial generation and release of ROS providing for IPC and antiarrhythmic activity.