Summary
The purpose of this investigation was to examine the effect of various lipophilic drugs on the cerebral hexokinase activity bound to the outer mitochondrial membrane. Experiments were carried out using a mitochondrial fraction from rat brain in vitro and cortex from an isolated perfused rat brain preparation, and from rat brain in vivo.
-
1.
Chlorpromazine, perphenazine, imipramine and desipramine, were used as highly lipophilic drugs. These drugs enhanced the binding of hexokinase activity to rat brain mitochondria in vitro. No effect on the intracellular hexokinase distribution was measurable in rat cortex in vivo after treatment with chlorpromazine and perphenazine. Chlorpromazine was also administered in a high concentration (100 μM) to the isolated perfused rat brain. A decrease of the soluble hexokinase activity in the cortex was determined in these experiments.
-
2.
Thiopental as well as the enantiomers of 1-methyl-5-phenyl-5-propylbarbituric acid were investigated. All barbiturates produced a solubilization of hexokinase activity from rat brain mitochondria in vitro. Administered to rats in vivo thiopental and the (R)(−)-enantiomer induced anesthesia and an increase of the soluble hexokinase activity in the cortex. However, the (S)(+)-enantiomer caused convulsions, and no increase of the soluble hexokinase actvity in cortical tissue was measurable.
-
3.
Amphetamine, morphine, phenytoin, and tetracaine enhanced the mitochondrial binding of hexokinase activity in vitro. Ethanol and phenytoin increased the soluble hexokinase activity in rat cortex in vivo. Phenylbutazone solubilized hexokinase activity in vitro only.
-
4.
From these results it may be suggested that only anesthetics applied in a therapeutic dosage range solubilize cerebral hexokinase activity from mitochondria in vivo and in vitro.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Andjus, R. K., Suhara, K., Sloviter, H. A.: An isolated perfused rat brain preparation, its spontaneous and stimulated activity. J. appl. Physiol. 22, 1033–1039 (1967)
Bielicki, L., Krieglstein, J.: Solubilization of brain mitochondrial hexokinase by thiopental. Naunyn-Schmiedeberg's Arch. Pharmacol. 298, 61–65 (1977a)
Bielicki, L., Krieglstein, J.: The effect of anesthesia on brain mitochondrial hexokinase. Naunyn-Schmiedeberg's Arch. Pharmacol. 298, 229–233 (1977b)
Bruns, H., Krieglstein, J., Wever, K.: Anesthesia and intracellular distribution of cerebral hexokinase. Anaesthesist 28, 557–561 (1978)
Fleck, W., Krieglstein, J., Urban, W.: Zwei Apparaturen zur Perfusion des isolierten Rattenhirns. Arzneimittel-Forsch. 22, 1225–1230 (1972)
Knabe, J., Rummel, W., Büch, H. P., Franz, N.: Optically active barbiturates-synthesis, configuration and pharmacological effects. Arzneimittel-Forsch. 28, 1048–1056 (1978)
Knull, H. R., Tylor, W. F., Wells, W. W.: Effects of energy metabolism on in vivo distribution of hexokinase in brain. J. Biol. Chem. 218, 5414–5417 (1973)
Krieglstein, J., Bielicki, L.: The influence of thiopental on the intracellular distribution of hexokinase in rat brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 293, R 11 (1976)
Sachs, L.: Angewandte Statistik. 4th ed. Berlin, Heidelberg, New York: Springer 1974
Seeman, P.: The membrane actions of anesthetics and tranquilizers. Pharmacol. Rev. 24, 583–655 (1972)
Seeman, P., Kwant, W. O.: Membrane expansion of the eythrocyte by both the neutral and ionized forms of chlorpromazine. Biochim. Biophys. Acta 183, 512–519 (1969)
Wilson, J. E.: The latent hexokinase activity of rat brain mitochondria. Biochim. Biophys. Res. Commun. 28, 123–127 (1967)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hanke, J., Höfeler, H., Krieglstein, J. et al. Influence of various lipophilic drugs on brain mitochondrial hexokinase. Naunyn-Schmiedeberg's Arch. Pharmacol. 307, 171–176 (1979). https://doi.org/10.1007/BF00498460
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00498460