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.
|
Authors | T Martinsson, C J Fowler |
Journal | Life sciences
(Life Sci)
Vol. 53
Issue 20
Pg. 1557-65
( 1993)
ISSN: 0024-3205 [Print] Netherlands |
PMID | 8412521
(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)
|