Effect of methohexital on the relationship between hexokinase distribution and energy metabolism in neuroblastoma cells.

Cultured neuroblastoma cells (clone neuro-2a) were used to demonstrate the influence of an anesthetic on energy metabolism by acting on the intracellular distribution of hexokinase activity. First of all, there was to be shown that a relationship between the intracellular hexokinase distribution and energy metabolism actually exists in neuroblastoma cells. Since glucose-6-phosphate could be assumed to be the main regulator of this enzyme distribution, experimental conditions were chosen where the glucose-6-phosphate level was changed significantly. A decrease in the glucose-6-phosphate level in the cells was achieved by deprivation of glucose and oxygen for 30 min. Under these conditions the glucose-6-phosphate level and the soluble hexokinase activity decreased significantly. The effect was reversible when glucose and oxygen were again added to the incubation medium of the cells. On the other hand, the antimetabolite 6-aminonicotinamide produced an accumulation of glucose-6-phosphate which caused an increase in the soluble hexokinase activity. These results brought evidence for a correlation of intracellular hexokinase distribution and energy metabolism. When alpha-(+/-)-5-allyl-1-methyl-5-(1-methyl-2-pentinyl) barbituric acid (methohexital) was added to the incubation medium of the neuroblastoma cells, a dose-dependent increase in soluble hexokinase activity was measurable, whereas the glucose-6-phosphate level was decreased at least within a therapeutically relevant dosage range of the anesthetic. This effect was reversible when methohexital was washed out from the cells.(ABSTRACT TRUNCATED AT 250 WORDS)