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Local anaesthetics do not affect protein kinase C function in intact neuroblastoma cells.

Abstract
The effects of local anaesthetics on protein kinase C function in vitro were examined in two model systems: differentiation in mouse Neuro-2a neuroblastoma cells and muscarine M1-receptor mediated phosphoinositide breakdown in human SK-N-MC neuroblastoma cells. Staurosporin, a protein kinase C inhibitor, induced marked neuritogenesis in Neuro-2a cells after incubation for 5 h, whereas no effect could be seen after exposure to the local anaesthetics ropivacaine, lidocaine or bupivacaine. In the other model, protein kinase C-mediated regulation of phospholipase C was demonstrated for SK-N-MC cells. Phorbol 12-myristate 13-acetate, a protein kinase C activator, produced a dose-dependent decrease in both basal and carbachol-stimulated phosphoinositide breakdown. Staurosporin blocked this phorbol ester-induced subsensitivity completely, while ropivacaine, lidocaine or bupivacaine did not, suggesting that no functional protein kinase C antagonism is mediated by local anaesthetics. The present study suggests that unlike the reported inhibiting effects of local anaesthetics on purified protein kinase C isoforms, no such modulation is found in intact neuroblastoma cells.
AuthorsT Martinsson, C J Fowler
JournalLife sciences (Life Sci) Vol. 53 Issue 20 Pg. 1557-65 ( 1993) ISSN: 0024-3205 [Print] Netherlands
PMID8412521 (Publication Type: Journal Article)
Chemical References
  • Alkaloids
  • Anesthetics, Local
  • Phosphatidylinositols
  • Receptors, Muscarinic
  • Protein Kinase C
  • Staurosporine
Topics
  • Alkaloids (pharmacology)
  • Anesthetics, Local (pharmacology)
  • Animals
  • Cell Differentiation (drug effects)
  • Humans
  • Mice
  • Models, Biological
  • Neurites (drug effects)
  • Neuroblastoma (enzymology, metabolism, pathology)
  • Phosphatidylinositols (metabolism)
  • Protein Kinase C (drug effects, physiology)
  • Receptors, Muscarinic (drug effects, physiology)
  • Staurosporine
  • Tumor Cells, Cultured (drug effects)

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