title: Role of intracellular Cd2+ in catecholamine release and lethality in PC12 cells.
abstract: To evaluate the role of intracellular Cd2+ in catecholamine release and lethality in rat pheochromocytoma (PC12) cells the following results were obtained: [1] the presence of Cd2+ intracellularly was demonstrated with the Cd(2+)-sensitive fluorescent dye BTC-5N, [2] Cd2+ entry through Ca(2+)-channels was either blocked with nifedipine or diltiazem or increased with Bay K8644, [3] Cd2+ entry through voltage sensitive Ca2+ channels was related to dopamine release and cell lethality, [4] a calmodulin inhibitor protected against Cd2+ toxicity, and [5] extracellular Ca2+ concentration, altered prior to Cd2+ exposure, was inversely related to dopamine release by Cd2+. The data indicate intracellular effects of Cd2+ rather than cell surface actions are primarily involved in neurotransmitter release and lethality by toxic levels of Cd2+ in adrenomedullary cells. To evaluate the role of intracellular Cd2+ in catecholamine release and lethality in rat pheochromocytoma (PC12) cells the following results were obtained: [1] the presence of Cd2+ intracellularly was demonstrated with the Cd(2+)-sensitive fluorescent dye BTC-5N, [2] Cd2+ entry through Ca(2+)-channels was either blocked with nifedipine or diltiazem or increased with Bay K8644, [3] Cd2+ entry through voltage sensitive Ca2+ channels was related to dopamine release and cell lethality, [4] a calmodulin inhibitor protected against Cd2+ toxicity, and [5] extracellular Ca2+ concentration, altered prior to Cd2+ exposure, was inversely related to dopamine release by Cd2+. The data indicate intracellular effects of Cd2+ rather than cell surface actions are primarily involved in neurotransmitter release and lethality by toxic levels of Cd2+ in adrenomedullary cells.
authors.affiliation: Department of Pharmacology and Toxicology, Purdue University, West Lafayette, IN 47907-1334, USA.
authors.forename: A G
authors.initials: AG
authors.lastname: Kanthasamy
authors.forename: G E
authors.initials: GE
authors.lastname: Isom
authors.forename: J L
authors.initials: JL
authors.lastname: Borowitz
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D002104:Cadmium / Q000378:metabolism* / Q000633:toxicity*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats
chemical_list: D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002104:Cadmium; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D004298:Dopamine