LOCAL-ANESTHETICS DO NOT AFFECT PROTEIN-KINASE-C FUNCTION IN INTACT NEUROBLASTOMA-CELLS

The effects of local anaesthetics on protein kinase C function in vitr o were examined in two model systems: differentiation in mouse Neuro-2 a neuroblastoma cells and muscarine M1-receptor mediated phosphoinosit ide breakdown in human SK-N-MC neuroblastoma cells . Staurosporin, a p rotein kinase C inhibitor, induced marked neuritogenesis in Neuro-2a c ells after incubation for 5 h, whereas no effect could be seen after e xposure to the local anaesthetics ropivacaine, lidocaine or bupivacain e. In the other model, protein kinase C-mediated regulation of phospho lipase C was demonstrated for SK-N-MC cells. Phorbol 12-myristate 13-a cetate, a protein kinase C activator, produced a dose-dependent decrea se in both basal and carbachol-stimulated phosphoinositide breakdown. Staurosporin blocked this phorbol ester-induced subsensitivity complet ely, while ropivacaine, lidocaine or bupivacaine did not, suggesting t hat no functional protein kinase C antagonism is mediated by local ana esthetics. The present study suggests that unlike the reported inhibit ing effects of local anaesthetics on purified protein kinase C isoform s, no such modulation is found in intact neuroblastoma cells.