Accumulation of labeled cyanide in neuronal tissue.
Since cyanide is a reactive chemical substance and has the potential of forming a variety of adducts in biological systems, the rate of accumulation of labeled cyanide was studied in neural tissue, a major target for the toxic action of cyanide. Accumulation of 14CN in mouse brain slices and in rat pheochromocytoma (PC12) cells was about five times more rapid in the first few minutes than at later times. In both tissues, incubation at low temperature (4 degrees C) decreased the secondary phase without affecting the initial phase. In PC12 cells, determination of the subcellular distribution of cyanide revealed that the cytoplasmic fraction was the least sensitive to temperature and therefore may represent the initial rapid phase of cyanide accumulation. Accumulation of cyanide in mitochondrial and microsomal fractions was temperature sensitive. Cyanide accumulation is proportional to the concentration in the medium (0.1-1 mM) in both mouse brain and PC12 cells suggesting that the cyanide sinks in neural tissue have a large capacity and are nonspecific. Cyanide interaction with neural tissue is not uniform since cyanide accumulated more in hypothalamus than in other brain areas. Despite this, mitochondrial enzyme activity was no greater in hypothalamus than in other brain areas. No increase in thiocyanate, the main metabolite of cyanide, could be detected in brain tissue incubated 30 min with 1 mM cyanide, showing that accumulated 14C is not in the form of thiocyanate. Cyanide appears to equilibrate rapidly across the plasma membrane and then slowly accumulates in mitochondria and membrane elements of the neuronal cell. Competition for cyanide among subcellular elements may be a factor in the toxic action of cyanide.
Borowitz
J L
JL
Department of Pharmacology and Toxicology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907-1334.
Rathinavelu
A
A
Kanthasamy
A
A
Wilsbacher
J
J
Isom
G E
GE
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003486:Cyanides / Q000097:blood / Q000378:metabolism* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007553:Isotope Labeling; D008297:Male; D051379:Mice; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D013696:Temperature; D013861:Thiocyanates / Q000378:metabolism
D002250:Carbon Radioisotopes; D003486:Cyanides; D013861:Thiocyanates; C031760:thiocyanate