Summary
Concentrations and specific radioactivities of choline, acetylcholine, phosphorylcholine, lipid choline, and sn-glycero-3-phosphorylcholine after i.v. injection of methyl-14C-choline were measured in the brain of untreated controls and of rats anesthesized with urethane.
The specific activity was found to be decreased during deep anesthesia by 40% in acetylcholine, 20–30% in phosphorylcholine, 50–75% in lipid choline, and 30–40% in sn-glycero-3-phosphorylcholine. No significant change was detected in the specific activity of choline. The brain concentration of acetylcholine was increased by 40%, the concentration of sn-glycero-3-phosphorylcholine, however, was diminished by 10% during anesthesia. No change was found in the concentration of the other choline containing compounds investigated.
Measuring choline incorporation into 4 subcellular fractions of brain tissue specific activities were found to be decreased by the same percentage, although 2 fractions (nuclei and microsomes) were higher labelled than the 2 other fractions (crude mitochondria with synaptosomes and lysosomes).
A correlation between the biochemical and the functional alterations is supported by the dose-effect relationships on both parameters.
It is suggested that urethane reduces turnover of lipids and by that mechanism inhibits the exocytotic release of the transmitter from presynaptic nerve endings.
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Anderson, E. G., Bonnycastle, D. D.: A study of the central depressant action of pentobarbital, phenobarbital and diethyl ether in relationship to increase in brain 5-hydroxytryptamine. J. Pharmacol. Exp. Ther. 130, 138–140 (1960)
Ansell, G. B., Dohmen, H.: The metabolism of individual phospholipids in the rat brain during hypoglycaemia, anaesthesia and convulsions. J. Neurochem. 2, 1–10 (1957)
Aquilonius, S.-M., Flentge, F., Schuberth, J., Sparf, B., Sundwall, A.: Synthesis of acetylcholine in different compartment of brain nerve terminals in vivo as studied by the incorporation of choline from plasma and the effect of pentobarbital on this process. J. Neurochem. 20, 1509–1521 (1973)
Bourgoin, S., Ternaux, J. B., Boireau, A., Héry, F., Hamon, M.: Effects of halothane and nitrous oxide anaesthesia on 5-HT turn-over in the rat brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 288, 109–121 (1975)
Cooke, C. T., Nolan, T. M., Dyson, S. E., Jones, D. G.: Phenobarbital-induced configurational changes at the synapse. Brain Res. 76, 330–335 (1974)
Corrodi, H., Fuxe, K., Höckfelt, T.: The effects of barbiturates on the activity of the catecholamine neurones in the rat brain. J. Pharm. Pharmacol. 18, 556–558 (1966)
Dawson, R. M. C., Richter, D.: The phosphorus metabolism of the brain. Proc. Roy. Soc. 137, 252–257 (1950)
Dross, K., Kewitz, H.: Der Einbau von Cholin in das Acetylcholin während der Narkose und bei der DFP-Vergiftung. Naunyn-Schmiedebergs Arch. Pharmakol. exp. Path. 257, 13 (1967)
Dross, K., Kewitz, H.: Concentration and origin of choline in the rat brain. Naunyn-Schmiedeberg's Arch. Pharmakol. 274, 91–106 (1972)
Elliott, K. A. C., Swank, R. L., Henderson, N.: Effects of anaesthetic and convulsants on acetylcholine content in brain. Am. J. Physiol. 162, 469–474 (1950)
Gatfield, P. D., Lowry, O. H., Schultz, D. W., Passonneau, J. V.: Regional energy reserves in mouse brain and changes with ischaemia and anaesthesia. J. Neurochem. 13, 185–195 (1966)
Herken, H., Neubert, D.: Der Acetylcholingehalt des Gehirns bei verschiedenen Funktionszuständen. Naunyn-Schmiedebergs Arch. exp. Path. Pharmakol. 219, 223–233 (1953)
Kewitz, H.: Der Nachweis von 4-Amino-n-Buturylcholin im Warmblütergehirn. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 237, 308–318 (1959)
Kewitz, H., Pleul, O.: Synthesis of choline from ethanolamine in rat brain. Proc. Nat. Acad. Sci. U.S.A. 73, 2181–2185 (1976)
Kewitz, H., Pleul, O., Dross, K., Schwartzkopff, T.: The supply of choline in brain. In: Cholinergic Mechanisms (G. P. Waser, ed.), pp. 131–135. New York: Raven Press 1975
Klöppel, A., Post, D., Schneider, G., Schütz, H.: Abtrennung quartäter Ammoniumverbindungen über zerlegbare Ionenpaarextrakte mit nachfolgender Identifizierung. Fresenius Z. Anal. Chem. 252, 279–284 (1970)
MacIntosh, F. C., Perry, W. L. M.: Biological estimation of acetylcholine. Methods Med. Res. 3, 78–92 (1950)
Mitchell, J. F.: The spontaneous and evoked release of acetylcholine from the cerebral cortex. J. Physiol. (Lond.) 165, 98–116 (1963)
Modak, A. T., Weintraub, S. T., McCoy, T. H., Stavinoha, W. B.: Use of 300-msec microwave irradiation for enzyme inactivation: a study of effects of sodium pentobarbital on acetylcholine concentration in mouse brain regions. J. Pharmacol. Exp. Ther. 197, 245–252 (1976)
Mück, R.: Inkorporation von 14C-Cholin in die Phospholipide von Herz, Muskel und Lunge und ihre Beeinflussung durch Vorbehandlung mit Phenobarbital und durch Urethannarkose. Inaugural Dissertation, Berlin 1975
Nordberg, A., Sundwall, A.: Effect of pentobarbital on endogenous acetylcholine and biotransformation of radioactive choline in different brain regions. In: Cholinergic Mechanisms, (P. G. Waser, ed.), pp. 229–239. New York: Raven Press 1975
Persson, T., Waldeck, B.: A reduced rate of turnover of brain noradrenaline during pentobarbitone anaesthesia. J. Pharm. Pharmacol. 23, 377–378 (1971)
De Robertis, E.: Electron microscope and chemical study of binding sites of brain biogenic amines. In: Progress in Brain Research, Vol. 8, Biogenic Amines (H. E. Himwich and W. A. Himwich, eds.), pp. 118–136. Amsterdam-London-New York: Elsevier 1964
Richter, D., Crossland, J.: Variation in acetylcholine content of the brain with physiological state. Am. J. Physiol. 159, 247–255 (1949)
Sawant, P. L., Shibko, S., Kumta, M. S., Tappel, A. L.: Isolation of rat-liver lysosomes and their general properties. Biochim. Biophys. Acta 85, 80–92 (1964)
Schill, G., Danielson, B.: Photometric determination of quaternary ammonium compounds with hexanitrodiphenylamine I. Anal. Chim. Acta 21, 248–254 (1959)
Schuberth, J., Sparf, B., Sundwall, A.: A technique for the study of acetylcholine turnover in mouse brain in vivo. J. Neurochem. 16, 695–700 (1969)
Stone, W. E.: Acetylcholine in brain. I. “Free”, “bound”, and total acetylcholine. Arch. Biochem. 59, 181–192 (1955)
Streit, P., Akert, K., Sandri, C., Livingstone, R. B., Moor, H.: Dynamic ultrastructure of presynaptic membranes at nerve terminals in the spinal cord of rats. Anesthesized and unanesthesized preparations compared. Brain Res. 48, 11–26 (1972)
Whittaker, V. P.: Investigation on the storage sites of biogenic amines in the central nervous system. In: Progress in Brain Research, Vol. 8, Biogenic Amines (H. E. Himwich and W. A. Himwich, eds.), pp. 90–117, Amsterdam-London-New York: Elsevier 1964
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Kewitz, H., Pleul, O. Inhibition of choline incorporation into brain lipids in rats by urethane, a proposed mechanism of depression of the central nervous system. Naunyn-Schmiedeberg's Arch. Pharmacol. 298, 205–210 (1977). https://doi.org/10.1007/BF00500888
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DOI: https://doi.org/10.1007/BF00500888