Possible Role of Opioids and KATP Channels in Neuroprotective Effect of Postconditioning in Mice

Abstract

The present study was designed to investigate the possible role of opioids and K ATP channels in ischemic postconditioning-induced reversal of global cerebral ischemia and reperfusion (I/R) induced neuronal injury. Mice were subjected to global ischemia by bilateral carotid artery occlusion for 10 min followed by reperfusion for 24 h, to produce neuronal injury. Ischemic postconditioning was induced by three episodes of carotid artery occlusion and reperfusion of 10 s each, immediately after global ischemia. Morphine postconditioning was induced by administration of morphine (5 mg/kg i.v.), 5 min prior to reperfusion. Naloxone (5 mg/kg i.v.), opioid receptor antagonist, and glibenclamide (5 mg/kg i.v.), K ATP channel blocker were administered 10 min before global ischemia. Extent of cerebral injury was assessed by measuring cerebral infarct size using triphenyl tetrazolium chloride (TTC) staining. Short-term memory was evaluated using the elevated plus maze test, while degree of motor incoordination was evaluated using inclined beam-walking, rota-rod and lateral push tests. Bilateral carotid artery occlusion followed by reperfusion resulted in significant increase in infarct size, impairment in short-term memory and motor co-ordination. Ischemic/morphine postconditioning significantly attenuated I/R induced neuronal injury and behavioural alterations. Pretreatments with naloxone and glibenclamide attenuated the neuroprotective effects of ischemic/morphine postconditioning. It may be concluded that ischemic/morphine postconditioning protects I/R induced cerebral injury via activating opioid receptor and K ATP channel opening.

Activation of the δ-opioid receptor inhibits serum deprivation-induced apoptosis of human liver cells via the activation of PKC and the mitochondrial pathway

“…It has been confirmed that opioid receptors act through the PTX-sensitive G protein signal pathway (35) and the KATP signal pathway (36). In addition, Zhao et al (37) found that opioid receptors promote cell survival and proliferation via the ERK1/2 pathway.…”

Modulation of Neuroprotective Effect of Ischemic Post-Conditioning by Dichlorobenzamil a Na+/Ca2+ Exchanger Inhibitor in Mice

“…7) Further, several recent-reports from our laboratory 8,9) as well as from others [10][11][12] have advocated cerebro-protective role of ischemic post-conditioning. The major advantage of post-conditioning is its clinical feasibility and it has been observed to produce tissue protective effects in various clinical settings.…”

Interaction of Risk Factors, Comorbidities, and Comedications with Ischemia/Reperfusion Injury and Cardioprotection by Preconditioning, Postconditioning, and Remote Conditioning

“…A subsequent study found that mice deficient for the myocardial adenosine A 2A receptor were resistant to ischemic postconditioning (Morrison et al, 2007). Since 2007, an increasing number of autacoid mediators of postconditioning have been described, including bradykinin (Penna et al, 2007;Xi et al, 2008), opioids (Jang et al, 2008;Pateliya et al, 2008;Zatta et al, 2008), TNFa (Lacerda et al, 2009), and sphingosine (Jin et al, 2008;Vessey et al, 2008a,b).…”