Distinct mechanisms of neurotransmitter release from PC 12 cells exposed to lead.
Two enzymes, protein kinase C and microsomal Ca(2+)-ATPase help regulate levels of Ca2+ in many types of cells. Since proteins that regulate Ca2+ often influence sensitivity to Pb2+, we determined the possible roles played by protein kinase C and microsomal Ca(2+)-ATPase for the Pb(2+)-evoked release of norepinephrine (NOR) in PC cells. NOR release was observed at 10 microM Pb2+ when PC 12 cells were stimulated with inhibitors of microsomal Ca(2+)-ATPase such as thapsigargin, cyclopiazonic acid, or 2,5-di-(t-butyl)-hydroquinone. At 5 microM, Pb2+ evoked the release of NOR in PC 12 cells stimulated with activators of protein kinase C such as phorbol 12-myristate 13-acetate (PMA) or (-)-7-octylindolactam. NOR release was observed at 1 microM Pb2+ in the presence of both PMA and thapsigargin. Ni2+ and Cd2+ blocked NOR release stimulated by Pb2+ in the presence of thapsigargin but not by PMA. NOR released by thapsigargin stimulation was not altered in PC 12 cells depleted of protein kinase C. Two proteins found in vesicles, chromogranin B and secretogranin-II were released with NOR. Our results indicate that in PC 12 cells, PB(2+)-evokes the release of neurotransmitters. Furthermore, thapsigargin and PMA increase the cell's sensitivity to Pb2+ by different pathways.
Bressler
J P
JP
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Belloni-Olivi
L
L
Forman
S
S
Goldstein
G W
GW
D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002273:Carcinogens / Q000494:pharmacology; D002864:Chromogranins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007854:Lead / Q000494:pharmacology*; D008024:Ligands; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D009479:Neuropeptides / Q000378:metabolism; D009532:Nickel / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism* / Q000493:pharmacokinetics; D016716:PC12 Cells / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D011493:Protein Kinase C / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D014316:Tritium
D015220:Calcium Channels; D002273:Carcinogens; D002864:Chromogranins; D004791:Enzyme Inhibitors; D008024:Ligands; D009479:Neuropeptides; D011506:Proteins; D002104:Cadmium; D014316:Tritium; D007854:Lead; D019284:Thapsigargin; D009532:Nickel; D011493:Protein Kinase C; D000252:Calcium-Transporting ATPases; D013755:Tetradecanoylphorbol Acetate; D009638:Norepinephrine