Cyanide-induced alteration of the adenylate energy pool in a rat neurosecretory cell line.
Cultures of a rat PC12 pheochromocytoma neurosecretory cell line were used to determine the responsiveness of oxidative energy status of isolated neuronal cells to cyanide exposure. Intracellular levels of ATP and its immediate metabolites, ADP and AMP, were measured in monolayer cultures of PC12 cells incubated for 0-30 min with KCN (10 mM). Over the period 2.5-30 min. cyanide treatment decreased ATP levels by 32-51% but ADP and AMP levels were not altered significantly. Additionally, ATP/ADP and ATP/AMP ratios were significantly reduced in KCN-intoxicated cells. These alterations in energy status may explain the prompt ablation of ion homeostasis reported previously in this model upon exposure to KCN. The energy-depleting actions of cyanide were not modified by pretreatment of cells with diltiazem, a calcium channel antagonist demonstrated to possess cytoprotective activity against histotoxic hypoxia induced by cyanide. Since PC12 cells rapidly respond to cyanide, with predictable depletions of the cell adenylate energy pool, this cell line can serve as a suitable in vitro model for studies of neurotoxicity involving ischemic/hypoxic conditions.
Maduh
E U
EU
Department of Pharmacology and Toxicology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, IN 47907.
Borowitz
J L
JL
Isom
G E
GE
D000227:Adenine Nucleotides / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004110:Diltiazem / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009490:Neurosecretory Systems / Q000187:drug effects* / Q000378:metabolism; D011190:Potassium Cyanide / Q000037:antagonists & inhibitors / Q000633:toxicity*; D051381:Rats; D014407:Tumor Cells, Cultured
D000227:Adenine Nucleotides; D004110:Diltiazem; D011190:Potassium Cyanide