[Effect of local anesthetics on intracellular calcium messenger system]

Local anesthetics have been shown to affect a variety of cellular activities, such as exocytosis, membrane transport, permeability of calcium, and platelet aggregation, among others. Despite the disparate nature of the above phenomena, the calcium ion is essential for all of these cellular processes. Recently, it has been shown that local anesthetics inhibit specific calmodulin-dependent enzymes and protein kinase C-dependent enzymes. Therefore, the mode of action of local anesthetics in the activation of guinea pig neutrophils was examined in this study in order to understand the effect of local anesthetics on the intracellular calcium messenger system. In the presence of calmodulin inhibitors, FMLP-induced chemotaxis and superoxide anion production were strongly suppressed, whereas 1-oleoyl-2-acetylglycerol(OAG)(a direct activator of protein kinase C)-induced superoxide anion production was not affected. In contrast, protein kinase C inhibitors suppressed OAG-induced superoxide anion production but no inhibiting effect on FMLP-induced chemotaxis and superoxide anion production. Local anesthetics suppressed both FMLP- and OAG-induced activation of guinea pig neutrophils. These findings suggest that the inhibiting effect of local anesthetics on the activation of the intracellular calcium messenger system may be part of the pharmacological mechanism of local anesthetics in cellular activities.