Local anaesthetics do not affect protein kinase C function in intact neuroblastoma cells.
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.
Martinsson
T
T
Astra Pain Control AB, Preclinical R & D, Huddinge, Sweden.
Fowler
C J
CJ
D000470:Alkaloids / Q000494:pharmacology; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D006801:Humans; D051379:Mice; D008954:Models, Biological; D016501:Neurites / Q000187:drug effects; D009447:Neuroblastoma / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D010716:Phosphatidylinositols / Q000378:metabolism; D011493:Protein Kinase C / Q000187:drug effects* / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology; D019311:Staurosporine; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000470:Alkaloids; D000779:Anesthetics, Local; D010716:Phosphatidylinositols; D011976:Receptors, Muscarinic; D011493:Protein Kinase C; D019311:Staurosporine