Distinct mechanisms of neurotransmitter release from PC 12 cells exposed to lead

Joseph Bressler, Luisa Belloni-Olivi, Sheila Forman, Gary William Goldstein

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)678-685
Number of pages8
JournalJournal of Neuroscience Research
Volume46
Issue number6
DOIs
StatePublished - 1996

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Neurotransmitter Agents
Thapsigargin
Norepinephrine
Protein Kinase C
Calcium-Transporting ATPases
Acetates
Secretogranin II
Chromogranin B
Proteins
phorbol-12-myristate
Enzymes

Keywords

  • lead
  • neurotransmitter release
  • PC 12 cells

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Distinct mechanisms of neurotransmitter release from PC 12 cells exposed to lead. / Bressler, Joseph; Belloni-Olivi, Luisa; Forman, Sheila; Goldstein, Gary William.

In: Journal of Neuroscience Research, Vol. 46, No. 6, 1996, p. 678-685.

Research output: Contribution to journalArticle

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