title: Morphine prevents glutamate-induced death of primary rat neonatal astrocytes through modulation of intracellular redox.
abstract: This study is designed to investigate the effect of morphine on glutamate-induced toxicity of primary rat neonatal astrocytes. Glutamate decreases the intracellular GSH level, and thereby induces cytolysis of astrocytes and C6 glial cells accompanied by apoptotic features. Glutamate-induced cytotoxicity is protected by morphine and antioxidants such as GSH and NAC, whereas MK-801, an antagonist of glutamate receptor NMDA does not protect astrocytes against glutamate toxicity. Also, morphine antagonist, naloxone, as well as selective ligands for opioid receptor subtypes, including DAMGO, DPDPE, and U69593, do not inhibit the protective effect of morphine on glutamate-induced cytotoxicity. Morphine significantly prevents the depletion of GSH by glutamate and thereby inhibits the generation of H2O2 in a dose-dependent manner. Furthermore, morphine prevents the change of mitochondrial permeability transition by glutamate. Taken together, we suggest that morphine protects the primary rat neonatal astrocytes from glutamate toxicity via modulation of intracellular redox status.
authors.affiliation: Department of Microbiology, Vestibulocochlear Research Center, University of Wonkwang, Iksan, Jeonbuk, South Korea.
authors.forename: Jienny
authors.initials: J
authors.lastname: Lee
authors.forename: Myung-Sunny
authors.initials: MS
authors.lastname: Kim
authors.forename: Channy
authors.initials: C
authors.lastname: Park
authors.forename: Eun-Bae
authors.initials: EB
authors.lastname: Jung
authors.forename: Duk-Hwa
authors.initials: DH
authors.lastname: Choi
authors.forename: Tae-Yo
authors.initials: TY
authors.lastname: Kim
authors.forename: Sung-Keun
authors.initials: SK
authors.lastname: Moon
authors.forename: Raekil
authors.initials: R
authors.lastname: Park
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D044482:Benzeneacetamides / Q000494:pharmacology; D001562:Benzimidazoles / Q000737:chemistry; D006690:Bisbenzimidazole / Q000737:chemistry; D002232:Carbocyanines / Q000737:chemistry; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016291:Dizocilpine Maleate / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism; D007473:Ion Channels / Q000187:drug effects; D008856:Microscopy, Fluorescence; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D020112:Rhodamine 123 / Q000737:chemistry
chemical_list: D044482:Benzeneacetamides; D001562:Benzimidazoles; D002232:Carbocyanines; D007473:Ion Channels; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D009292:Narcotic Antagonists; D011759:Pyrrolidines; D016194:Receptors, N-Methyl-D-Aspartate; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020112:Rhodamine 123; C068624:5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine; D009270:Naloxone; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-; D006861:Hydrogen Peroxide; D005978:Glutathione; C045444:U 69593; D006690:Bisbenzimidazole; D000111:Acetylcysteine