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Opioid Receptor-independent Protection of Ischemic Rat Hepatocytes by Morphine

Overview
Publisher Elsevier
Specialty Biochemistry
Date 2006 Nov 14
PMID 17097606
Citations 3
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Abstract

We studied the role of morphine in anoxia/reoxygenation injury to hepatocytes. Overnight cultured rat hepatocytes were incubated in anoxic buffer at pH 6.2 for 4h and reoxygenated at pH 7.4 for 2h to simulate anoxia/reoxygenation. Some hepatocytes were preincubated with 50 microM morphine for 10 min prior to onset of anoxia/reoxygenation. To study the effect of morphine on nitric oxide (NO), hepatocytes were loaded with 4-amino-5-methylamino-2',7'-difluorofluorescein (DAF-FM). Changes in NO concentration were assessed with a multi-well fluorescence reader and confocal microscopy. Morphine substantially improved cell viability after reoxygenation and increased NO generation, which was blocked by ATP-sensitive potassium channel blockers. Confocal images revealed that the increase in NO occurred mainly at the cytosol. However, treatment with opioid receptor antagonists did not reverse cytoprotection by morphine. These results indicate that morphine prevents anoxia/reoxygenation injury to hepatocytes. Protective mechanisms are associated with the potassium channels and NO, but are independent of opioid receptor-mediated signaling.

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References
1.
Rakhit R, Mojet M, Marber M, Duchen M . Mitochondria as targets for nitric oxide-induced protection during simulated ischemia and reoxygenation in isolated neonatal cardiomyocytes. Circulation. 2001; 103(21):2617-23. DOI: 10.1161/01.cir.103.21.2617. View

2.
Fryer R, Hsu A, Gross G . ERK and p38 MAP kinase activation are components of opioid-induced delayed cardioprotection. Basic Res Cardiol. 2001; 96(2):136-42. DOI: 10.1007/s003950170063. View

3.
Wang Y, Guo Y, Zhang S, Wu W, Wang J, Bao W . Ischemic preconditioning upregulates inducible nitric oxide synthase in cardiac myocyte. J Mol Cell Cardiol. 2002; 34(1):5-15. DOI: 10.1006/jmcc.2001.1482. View

4.
Gumpricht E, Dahl R, Yerushalmi B, Devereaux M, Sokol R . Nitric oxide ameliorates hydrophobic bile acid-induced apoptosis in isolated rat hepatocytes by non-mitochondrial pathways. J Biol Chem. 2002; 277(28):25823-30. DOI: 10.1074/jbc.M112305200. View

5.
Kim J, Qian T, Lemasters J . Mitochondrial permeability transition in the switch from necrotic to apoptotic cell death in ischemic rat hepatocytes. Gastroenterology. 2003; 124(2):494-503. DOI: 10.1053/gast.2003.50059. View