TY - JOUR
T1 - Distinct mechanisms of neurotransmitter release from PC 12 cells exposed to lead
AU - Bressler, Joseph P.
AU - Belloni-Olivi, Luisa
AU - Forman, Sheila
AU - Goldstein, Gary W.
PY - 1996
Y1 - 1996
N2 - Two enzymes, protein kinase C and microsomal Ca2+-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 Ca2+-ATPase for the Pb2+- evoked release of norepinephrine (NOR) in PC 12 cells. NOR release was observed at 10 μM Pb2+ when PC 12 cells were stimulated with inhibitors of microsomal Ca2+-ATPase such as thapsigargin, cyclopiazonic acid, or 2,5- di-(t-butyl)-hydroquinone. At 5 μM, 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 μM 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, Pb2+-evokes the release of neurotransmitters. Furthermore, thapsigargin and PMA increase the cell's sensitivity to Pb2+ by different pathways.
AB - Two enzymes, protein kinase C and microsomal Ca2+-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 Ca2+-ATPase for the Pb2+- evoked release of norepinephrine (NOR) in PC 12 cells. NOR release was observed at 10 μM Pb2+ when PC 12 cells were stimulated with inhibitors of microsomal Ca2+-ATPase such as thapsigargin, cyclopiazonic acid, or 2,5- di-(t-butyl)-hydroquinone. At 5 μM, 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 μM 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, Pb2+-evokes the release of neurotransmitters. Furthermore, thapsigargin and PMA increase the cell's sensitivity to Pb2+ by different pathways.
KW - PC 12 cells
KW - lead
KW - neurotransmitter release
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U2 - 10.1002/(SICI)1097-4547(19961215)46:6<678::AID-JNR5>3.0.CO;2-C
DO - 10.1002/(SICI)1097-4547(19961215)46:6<678::AID-JNR5>3.0.CO;2-C
M3 - Article
C2 - 8978502
AN - SCOPUS:0030448818
SN - 0360-4012
VL - 46
SP - 678
EP - 685
JO - Journal of neuroscience research
JF - Journal of neuroscience research
IS - 6
ER -