Mitochondrial inhibitors evoke catecholamine release from pheochromocytoma cells.
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.
Taylor
S C
SC
Institute for Cardiovascular Research, University of Leeds, Leeds, LS2 9JT, United Kingdom.
Shaw
S M
SM
Peers
C
C
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*
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