STAUROSPORINE, A PROTEIN-KINASE-C INHIBITOR, DECREASES THE GENERAL ANESTHETIC REQUIREMENT IN RANA-PIPIENS TADPOLES

Protein kinase C, the intracellular effector for the inositol phosphat e-mediated signal transduction pathway, plays a key role in neurotrans mission in the central nervous system. Although the in vitro activity of protein kinase C is inhibited by therapeutic concentrations of vola tile anesthetics, the relation of this effect to in vivo obtundation h as not been established. If obtundation by volatile anesthetics involv es protein kinase C inhibition, then an inhibitor of this enzyme shoul d decrease the anesthetic requirement. To test this hypothesis, we com pared the EC50s of halothane and diethylether for loss of the righting reflex in Rana pipiens tadpoles pretreated with staurosporine and in untreated controls. Anesthetic concentrations were confirmed by gas ch romatography and staurosporine concentrations by ultraviolet absorbanc e spectrophotometry Results obtained in more than 1000 animals indicat ed that pretreatment with staurosporine concentrations in the nanomola r range significantly decreased the EC50 for both halothane (68% of co ntrol; P < 0.035) and diethylether (41% of control; P < 0.001). This f inding implies that protein kinase C inhibition may play a role in gen eral anesthetic-induced obtundation.