Attenuation of potassium cyanide-mediated neuronal cell death by adenosine.
Glutamate has been shown to play an important role in delayed neuronal cell death occurring due to ischemia. Attenuation of synaptically released glutamate can be accomplished by modulators such as adenosine and baclofen. This study focused on the ability of adenosine to attenuate the excitotoxicity secondary to glutamate receptor activation in vitro after exposure to potassium cyanide (KCN) in hippocampal neuronal cell cultures. For this study, hippocampal cell cultures were obtained from 1-day-old rats and trypan blue staining was used for assessment of cell viability. It was found that the N-methyl-D-aspartate-specific antagonist MK801 (10 microM) attenuated neuronal cell death resulting from exposure to 1 mM KCN for 60 minutes. Adenosine (10 to 1000 microM) decreased neuronal cell death secondary to the same concentration of KCN in a dose-dependent manner. This same neuroprotective effect is mimicked by the adenosine A1-specific receptor agonist N6-cyclopentyladenosine (10 microM). The A1-specific receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (10 to 1000 nM) blocked the neuroprotective effect of adenosine in a dose-dependent manner. Therefore, neuronal cell death produced by KCN in the experimental model described was mediated at least in part by glutamate. This neuronal cell death was attenuated by adenosine via the A1-specific mechanism.
Sturm
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CD
Division of Neurosurgery, St. Louis University School of Medicine, Missouri.
Frisella
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WA
Yoon
K W
KW
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D016291:Dizocilpine Maleate / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology; D009474:Neurons / Q000187:drug effects*; D009994:Osmolar Concentration; D011190:Potassium Cyanide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D058914:Purinergic Antagonists; D013805:Theobromine / Q000031:analogs & derivatives / Q000494:pharmacology; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology
D058914:Purinergic Antagonists; C053907:8-cyclopentyl-1,3-dimethylxanthine; C048599:N(6)-cyclopentyladenosine; C057837:3,7-dimethyl-1-propargylxanthine; D016291:Dizocilpine Maleate; D013806:Theophylline; D000241:Adenosine; D011190:Potassium Cyanide; D013805:Theobromine