Down-regulation or long-term inhibition of protein kinase C (PKC) reduces noradrenaline release evoked via either PKC-dependent or PKC-independent pathways in human SH-SY5Y neuroblastoma cells

Long-term (8–48 h) treatment of SH-SY5Y neuroblastoma cells with phorbol-12,13-dibutyrate (PDBu; 100 nM) promotes the down-regulation of protein kinase C (PKC) subtypes α and ϵ and reduces by up to 60% noradrenaline (NA) release evoked via both PKC-dependent (M 3-muscarinic receptor activation) and...

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Bibliographic Details
Published in:Neuroscience letters 1996-12, Vol.220 (1), p.37-40
Main Authors: Turner, Neil A., Walker, John H., Ball, Stephen G., Vaughan, Peter F.T.
Format: Article
Language:English
Subjects:
Biological and medical sciences
Carcinogens - pharmacology
Cell physiology
Down-Regulation
Fundamental and applied biological sciences. Psychology
Humans
Indoles - pharmacology
Maleimides - pharmacology
Molecular and cellular biology
Neuroblastoma
Noradrenaline release
Norepinephrine - pharmacokinetics
Phorbol 12,13-Dibutyrate - pharmacology
Phorbol ester
Protein kinase C
Protein Kinase C - antagonists & inhibitors
Protein Kinase C - metabolism
Secretion. Exocytosis
SH-SY5Y
Tumor Cells, Cultured
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Summary:Long-term (8–48 h) treatment of SH-SY5Y neuroblastoma cells with phorbol-12,13-dibutyrate (PDBu; 100 nM) promotes the down-regulation of protein kinase C (PKC) subtypes α and ϵ and reduces by up to 60% noradrenaline (NA) release evoked via both PKC-dependent (M 3-muscarinic receptor activation) and PKC-independent (depolarization) pathways, over similar time courses. A similar effect on release is observed following long-term (16–48 h) incubation with the PKC inhibitor Ro 31-7549 (10 μM), even after removal of the inhibitor, indicating a mechanism which is not rapidly reversible. Evidence is presented which suggests that long-term treatment with PDBu does not (1) affect calcium entry, (2) modulate levels of proteins important in the secretory mechanism or (3) reduce the number of secretory vesicles. Thus, the decrease in NA release in SH-SY5Y cells following down-regulation of PKC appears to be the result of a sustained reduction in PKC activity acting on a component of the secretory pathway not involved in the regulation of calcium entry or vesicle number.
ISSN:0304-3940
1872-7972
DOI:10.1016/S0304-3940(96)13245-6