title: Mitochondrial inhibitors evoke catecholamine release from pheochromocytoma cells.
abstract: Quantal catecholamine secretion evoked from individual pheochromocytoma (PC12) cells by exposure to mitochondrial inhibitors and uncouplers was monitored in real time using amperometry. Cyanide (0.05-5 mM) caused a concentration-dependent increase in the frequency of amperometric events. This secretory response was abolished by removal of extracellular Ca(2+) and by the application of Cd(2+) (200 microM), a nonselective blocker of voltage-gated Ca(2+) channels. Secretion was also inhibited by ca. 75% following pretreatment of cells with omega-conotoxin GVIA to inhibit N-type Ca(2+) channels selectively. Secretion was also detected when cells were exposed to rotenone (10 microM), dinitrophenol (250 microM) and p-trifluoromethoxyphenyl hydrazone (1 microM) and, as for cyanide, these secretory responses were abolished by removal of extracellular Ca(2+) or application of 200 microM Cd(2+). These results indicate that, like hypoxia, mitochondrial inhibitors and uncouplers evoke catecholamine secretion from PC12 cells which is wholly dependent on Ca(2+) influx through voltage-gated Ca(2+) channels.
authors.affiliation: Institute for Cardiovascular Research, University of Leeds, Leeds, LS2 9JT, United Kingdom.
authors.forename: S C
authors.initials: SC
authors.lastname: Taylor
authors.forename: S M
authors.initials: SM
authors.lastname: Shaw
authors.forename: C
authors.initials: C
authors.lastname: Peers
mesh_terms: D019297:2,4-Dinitrophenol / Q000494:pharmacology; D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D020864:Calcium Channels, N-Type / Q000378:metabolism; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism*; D015687:Cell Hypoxia / Q000502:physiology; D003486:Cyanides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D016716:PC12 Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D012402:Rotenone / Q000494:pharmacology; D014475:Uncoupling Agents / Q000494:pharmacology*
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D002395:Catecholamines; D003486:Cyanides; D014475:Uncoupling Agents; D002104:Cadmium; D012402:Rotenone; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D009543:Nifedipine; D019297:2,4-Dinitrophenol; D002118:Calcium