Summary
The purpose of the present investigation was to demonstrate that the distribution equilibrium between the less active soluble and the more active mitochondrial cerebral hexokinase is influenced by anesthesia. The following drugs were administered to male Sprague-Dawley rats to produce general anesthesia: phenobarbital (250 mg/kg), hexobarbital (200 mg/kg), chloral hydrate (350 mg/kg), ketamine (150 mg/kg), urethane (1.2 g/kg), halothane and ether. All drugs used caused a significant increase of the less active soluble form of hexokinase in brain. Incubation of mitochondrial hexokinase with anesthetics in vitro led, except with ketamine, to an increase of the soluble enzyme form. This indicates a possible direct action of drugs on the mitochondrial membrane; however an indirect effect mediated by physiological substrates is not excluded. The solubilization effect was well correlated with the stage of anesthesia. Changes in intracellular hexokinase distribution after halothane administration were already measurable at the time the righting reflex was lost and lasted as long as general anesthesia persisted. After injection of pentetrazol (150 mg/kg i.p.), rats anesthetized with phenobarbital (200 mg/kg i.p.) awoke within 4 min and the soluble hexokinase level had returned to the control range. Neither in vivo nor in vitro did the analeptic alone change the hexokinase distribution. In experiments with pentetrazol in vitro the solubilization of hexokinase by phenobarbital was also not influenced. These findings support the hypothesis that anesthetics may inhibit glucose phosphorylation in brain by solubilizing the more active mitochondrial hexokinase.
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Bielicki, L., Krieglstein, J.: Inhibition of glucose phosphorylation in rat brain by thiopental. Naunyn-Schmiedeberg's Arch. Pharmacol. 293, 25–29 (1976)
Bielicki, L., Krieglstein, J.: Solubilization of brain mitochondrial hexokinase by thiopental. Naunyn-Schmiedeberg's Arch. Pharmacol. 298, 61–65 (1977)
Crane, R. K., Sols, A.: The association of hexokinase with particulate fractions of brain and other tissue homogenates. J. biol. Chem. 203, 273–292 (1953)
Hein, H., Krieglstein, J., Stock, R.: The effect of increased glucose supply and thiopental anesthesia on energy metabolism of the isolated perfused rat brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 289, 399–407 (1975)
Hernandez, A., Crane, R. K.: Association of heart hexokinase with subcellular structure. Arch. Biochem. Biophys. 113, 223–229 (1966)
Johnson, M. K.: The intracellular distribution of glycolytic and other enzymes in rat brain homogenates and mitochondrial preparations. Biochem. J. 77, 610–618 (1960)
Karpatkin, S.: Soluble and particulate hexokinase of frog skeletal muscle. J. biol. Chem. 242, 3525–3530 (1967)
Knull, H. R., Taylor, W. F., Wells, W. W.: Effects of energy metabolism on in vivo distribution of hexokinase in brain. J. biol. Chem. 218, 5414–5417 (1973)
Knull, H. R., Taylor, W. F., Wells, W. W.: Insulin effects on brain energy metabolism and the related hexokinase distribution. J. biol. Chem. 249, 6930–6935 (1974)
Krieglstein, J., Bielicki, L.: The influence of thiopental on the intracellular distribution of hexokiase in rat brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 293, R11 (1976)
Krieglstein, J., Stock, R.: Comparative study of the effects of chloral hydrate and trichloroethanol on cerebral metabolism. Naunyn-Schmiedeberg's Arch. Pharmacol 277, 323–332 (1973)
Krieglstein, J., Stock, R.: Energy metabolism of the isolated perfused rat brain as influenced by anesthetics. Biochem. Pharmacol. 24, 1579–1582 (1975)
Kropp, E. S., Wilson, J. E.: Hexokinase binding sites on mitochondrial membranes. Biochem. biophys. Res. Commun. 38, 74–79 (1970)
McIlwain, H., Bachelard, H. S.: Biochemistry and the Central Nervous System. 4th ed. Edinburgh-London. Churchill Livingstone 1971
Richards, C. D.: Anesthetic mechanisms. Nature (Lond.) 262, 534 (1976)
Rose, J. A., Warms, J. V. B.: Mitochondrial hexokinase: release, rebinding and location. J. biol. Chem. 242, 1653–1654 (1967)
Tuttle, J. P., Wilson, J. E.: Rat brain hexokinase: A kinetic comparison of soluble and particulate forms. Biochim. biophys. Acta (Amst.) 212, 185–188 (1970)
Wever, K., Bielicki, L., Krieglstein, J.: Solubilization of brain mitochondrial hexokinase in anesthesia. Naunyn-Schmiedeberg's Arch. Pharmacol. 294, R 13 (1976)
Wilson, J. E.: The latent hexokinase activity of rat brain mitochondria. Biochem. biophys. Res. Commun. 28, 123–127 (1967)
Wilson, J. E.: Brain hexokinase. J. biol. Chem. 243, 3640–3647 (1968)
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The results have been briefly reported at the Pharmacology Meeting at Hannover (Wever et al., 1976)
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Bielicki, L., Krieglstein, J. The effect of anesthesia on brain mitochondrial hexokinase. Naunyn-Schmiedeberg's Arch. Pharmacol. 298, 229–233 (1977). https://doi.org/10.1007/BF00500892
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DOI: https://doi.org/10.1007/BF00500892