Summary
The purpose of the present investigation was to compare the solubilizing effect of methohexital on the mitochondrially bound hexokinase activity in brain and heart tissue of the rat. Experiments were performed using intact rats, the isolated perfused rat brain and heart as well as mitochondrial fractions from rat brain and heart tissue.
It was shown that bound hexokinase activity was significantly solubilized by methohexital in brain tissue in vivo and in the isolated perfused rat brain but no effect was demonstrable in heart tissue.
When mitochondrial fractions were incubated with methohexital in vitro, hexokinase activity was significantly solubilized from brain mitochondria but only slightly from heart mitochondria although glucose-6-phosphate was able to displace hexokinase also from heart mitochondria.
The results suggest that mitochondrially bound hexokinase activity in brain tissue is particularly sensitive against the solubilizing effect of anesthetics. This effect could contribute to the sensitivity of brain function and metabolism against anesthetic drugs.
Similar content being viewed by others
References
Andjus R, Suhara K, Sloviter HA (1967) An isolated, perfused rat brain preparation, its spontaneous and stimulated activity. J Appl Physiol 22:1033–1039
Bessman SP, Geiger PJ (1980) Compartimentation of hexokinase and creatine phosphokinase, cellular regulation, and insulin action. In: Horecker BL, Stadtman ER (eds) Current topics in cellular regulation. Academic Press, New York, pp 55–86
Bielicki L, Krieglstein J (1977a) Solubilization of brain mitochondrial hexokinase by thiopental. Naunyn-Schmiedeberg's Arch Pharmacol 298:61–65
Bielicki L, Krieglstein J (1977b) The effects of anesthesia on brain mitochondrial hexokinase. Naunyn-Schmiedeberg's Arch Pharmacol 298:229–233
Bruns H, Krieglstein J, Wever K (1978) Narkose und intrazelluläre Verteilung der Hexokinase. Anaesthesist 27:557–561
Dhalla NS, Yates JC, Walz DA, McDonald VA, Olson RE (1972) Correlation between changes in the endogenous energy stores and myocardial function due to hypoxia in the isolated perfused rat heart. Can J Physiol Pharmacol 50:333–345
Dirks B, Krieglstein J, Lind HH, Rieger H, Schütz H (1980) Fluorocarbon perfusion medium applied to the isolated rat brain. J Pharmacol Methods 4:95–108
England PJ, Randle PJ (1967) Effectors of rat-heart hexokinase and the control rates of glucose phosphorylation in the perfused rat heart. Biochem J 105:907–920
Hernandez A, Crane RK (1966) Association of heart hexokinase with subcellular structure. Arch Biochem Biophys 133:223–229
Inui M, Ishibashi S (1979) Functioning of mitochondrial-bound hexokinase in rat brain in accordance with generation of ATP inside the organelle. J Biochem (Tokyo) 85:1151–1156
Knull HR, Taylor WF, Wells WW (1973) Effects of energy metabolism on in vivo distribution of hexokinase. J Biol Chem 248:5414–5417
Krieglstein J, Sperling G, Twietmeyer G (1981) Effects of thiopental on regulatory mechanisms of brain energy metabolism. Naunyn-Schmiedeberg's Arch Pharmacol 318:56–61
Krieglstein J, Sperling G, Stock R (1982) Relationship between brain mitochondrial hexokinase and neuronal function. Comparable effects of 2-deoxy-D-glucose and thiopental. Neurochem Res 7:737–748
Wilson JE (1967) The latent hexokinase activity of rat brain mitochondria. Biochem Biophys Res Commun 28:123–127
Wilson JE (1980) Brain hexokinase, the prototype ambiquitous enzyme. In: Horecker BL, Stadtman ER (eds) Current topics in cellular regulation. Academic Press, New York, pp 1–44
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Karcher, L., Rachman, A. & Krieglstein, J. Comparison of rat brain and heart mitochondrial hexokinase solubilized by methohexital. Naunyn-Schmiedeberg's Arch. Pharmacol. 326, 80–82 (1984). https://doi.org/10.1007/BF00518783
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00518783