STAUROSPORINE, A PROTEIN-KINASE INHIBITOR, INCREASES THE INTOXICATINGPOTENCIES OF ETHANOL AND OTHER N-ALKANOLS IN RANA-PIPIENS TADPOLES

Central nervous system protein kinases are the intracellular effecters for many of the signal transduction pathways essential to neurotransm ission. Although the in vitro activity of at least one of these import ant enzymes, protein kinase C, is diminished by therapeutic concentrat ions of ethanol and other central depressants, the relationship of thi s effect to intoxication in vivo is not known. if intoxication by etha nol involves central protein kinase inhibition, then other inhibitors of these enzymes should enhance ethanol's intoxicating potency. To tes t this hypothesis, we compared the median effective concentrations of ethanol and two other n-alkanols for loss-of-righting reflex in Rana p ipiens tadpoles pretreated with staurosporine and in untreated control s. Alkanol concentrations were confirmed by gas chromatography and sta urosporine concentrations by ultraviolet absorbance spectrophotometry. Results obtained with 650 animals demonstrate that pretreatment with staurosporine concentrations in the nanomolar range significantly decr ease the median effective concentration for ethanol (56% of control; p < 0.001), butanol (38% of control; p < 0.001), and octanol (59% of co ntrol; p < 0.001). This finding supports that central protein kinase i nhibition may be involved in the acute intoxicating effects of ethanol and other n-alkanols.