Calcium mediation of cyanide-induced catecholamine release: implications for neurotoxicity.
Exposure of rat pheochromocytoma (PC12) cells to KCN (1.0-10 mM) over a 30-min period stimulated secretion of dopamine (DA) and decreased intracellular DA content. Addition of KCN (10 mM) to rat frontal cortex slices preloaded with 1-[7-3H]norepinephrine ([3H]NE) increased secretion of NE over a 10- to 30-min incubation period. In PC12 cells release of DA by KCN was nearly abolished in calcium-free media or by prior addition of diltiazem, a calcium channel antagonist. Release of [3H]NE from rat cortical slices by cyanide was only partly inhibited by diltiazem suggesting that intracellular calcium may be involved in this response. In PC12 cells KCN also produced a dose-related release of the DA precursor dihydroxyphenylalanine, without altering intracellular stores. Levels of the DA metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) were enhanced at lower concentrations of KCN. These observations indicate cyanide elicits exocytotic release of neurotransmitters in a calcium-dependent manner and also show that cyanide alters catecholamine metabolism. These actions of cyanide may be important in CNS symptoms of intoxication.
Kanthasamy
A G
AG
Department of Pharmacology and Toxicology, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette Indiana 47907.
Maduh
E U
EU
Peoples
R W
RW
Borowitz
J L
JL
Isom
G E
GE
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism*; D000310:Adrenal Gland Neoplasms; D000818:Animals; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D002460:Cell Line; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004110:Diltiazem / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004533:Egtazic Acid / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D009498:Neurotoxins; D009638:Norepinephrine / Q000378:metabolism*; D010673:Pheochromocytoma; D011190:Potassium Cyanide / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D009498:Neurotoxins; D015102:3,4-Dihydroxyphenylacetic Acid; D004533:Egtazic Acid; D004110:Diltiazem; D011190:Potassium Cyanide; D002118:Calcium; D004298:Dopamine; D009638:Norepinephrine