Summary
The effect of 6-aminonicotinamide (6-AN) on putative amino acid neurotransmitters, namely glutamate, GABA and aspartate was studied on brains of rats treated with this antimetabolite (35 mg/kg i.p.).
After 6-AN application the following substrates and metabolites were determined: phosphocreatine, ATP, ADP, AMP, glucose, glucose 6-phosphate, fructose 6-phosphate, pyruvate, lactate, α-ketoglutarate, glutamate, GABA, aspartate, ammonia, and 6-phosphogluconate.
The alterations in the cerebral energy metabolism were found as reported in the literature (increased levels of glucose, glucose 6-phosphate, decreased levels of lactate and pyruvate) and could be interpreted as the result of a reduced glycolytic flux rate.
After a prolonged period of 6-AN pretreatment (16–30 h) the GABA and glutamate concentrations were significantly reduced, whereas the level of aspartate remained unchanged.
From the results presented the two following conclusions may be drawn:
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a)
The changes in the concentration of neurotansmitters as GABA and glutamate could be resonsible for some neurological symptoms produced by 6-AN.
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b)
As 6-AN seems to affect the GABA-shunt it represents a model substance for studying this pathway in the nervous system.
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References
Baxter, C. F.: The nature of ψ-aminobutyric acid. In: Handbook of neurochemistry, vol. 3 (A. Lajtha, ed.), pp. 289–353. New York: Plenum Press, 1970
Bergmeyer, H. U.: Methoden der enzymatischen Analyse, 2. Aufl. Weinheim: Verlag Chemie 1970
Bielicki, L., Krieglstein, J.: Inhibition of glucose phosphorylation in rat brain by thiopental. Naunyn-Schmiedeberg's Arch. Pharmacol. 293, 25–29 (1976)
Brunnemann, A., Coper, H., Neubert, D.: Biosynthese und Wirkung des 6-Aminonicotinamid-adenindinucleotids (6-ANAD). Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 246, 437–451 (1964)
Graham, L. T., Aprison, M. H.: Fluorometric determination of aspartate, glutamate and ψ-aminobutyrate in nerve tissue using enzymic methods. Analyt. Biochem. 15, 487–497 (1966)
Herken, H., Keller, K., Kolbe, H., Lange, K., Schneider, H.: Experimentelle Myelopathie — Biochemische Grundlagen ihrer cellulären Pathogenese. Klin. Wschr. 51, 644–657 (1973)
Herken, H., Lange, K.: Blocking of pentose phosphate pathway in the brain of rats by 6-aminonicotinamide. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path. 263, 496–499 (1969)
Herken, H., Lange, K., Kolbe, H.: Brain disorders induced by pharmacological blockade of the pentose phosphate pathway. Biochem. biophys. Res. Commun. 36, 93–100 (1969)
Jacoby, W. B.: Methods of enzymology, Vol. 5 (S. P. Colowick and N. O. Kaplan, eds.), pp. 777–778 New York: Academic Press 1962
Johnson, W. J., McColl, J. D.: 6-Aminonicotinamide, a potent nicotinamide antagonist. Science 122, 834 (1955)
Kauffman, F. C., Johnson, E. C.: Cerebral energy reserves and glycolysis in neural tissue of 6-aminonicotinamide-treated mice. J. Neurobiol. 5, 379–392 (1974)
Keller, K., Kolbe, H., Lange, K., Herken, H.: Behaviour of the glycolytic system of rat brain and kidney in vivo after inhibition of the glucose-phosphate isomerase, II. Substrate concentrations under the influence of ischemia, 6-aminonicotinamide, and 2-deoxyglucose. Hoppe-Seylers Z. physiol. Chem. 353, 1389–1400 (1972)
Köhler, E., Barrach, H. J., Neubert, D.: Inhibition of NADP dependent oxidoreductases by the 6-aminonicotinamide analogue of NADP. FEBS Letters 6, 225–228 (1970)
Krieglstein, G., Krieglstein, J., Stock, R.: Suitability of the isolated perfused rat brain for studying effects on cerebral metabolism. Naunyn-Schmiedeberg's Arch. Pharmacol. 275, 124–134 (1972)
Krieglstein, J., Stock, R.: Decreased glycolytic flux rate in the isolated perfused rat brain after pretreatment with 6-aminonicotinamide. Naunyn-Schmiedeberg's Arch. Pharmacol. 290, 323–327 (1975)
Lange, K., Kolbe, H., Keller, K., Herken, H.: Der Kohlenhydratstoffwechsel des Gehirns nach Blockade des Pentose-PhosphatWeges durch 6-Aminonicotinsäureamid. Hoppe-Seylers Z. physiol. Chem. 351, 1241–1252 (1970)
McIlwain, H., Bachelard, H. S.: Biochemistry and the central nervous system. 4th edn. Edinburgh-London: Churchill Livingstone 1971
Neubert, D., Coper, H.: Die Geschwindigkeit der „malic enzyme” — Reaktion in Gegenwart von NADP-Analoga. Biochem. Z. 341, 485–494 (1965)
Schneider, H., Coper, H.: Morphologische Befunde am Zentralnervensystem der Ratte nach Vergiftung mit Antimetaboliten des Nicotinamids (6-Aminonicotinsäureamid und 3-Acetylpyridin) und einem Chinolinderivat (5-Nitro-8-hydroxychinolin). Arch. Psychiat. Nervenkr. 211, 138–154 (1968)
Sternberg, S. S., Philips, F. S.: 6-Aminonicotinamide and acute degenerative changes in the central nervous system. Science 127, 644–646 (1958)
Wolf, A., Cowen, D., Geller, L. M.: The effects of an antimetabolite, 6-aminonicotinamide, on the central nervous system. Trans. Amer. neurol. Ass. 84, 140–145 (1959)
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Bielicki, L., Krieglstein, J. Decreased GABA and glutamate concentration in rat brain after treatment with 6-aminonicotinamide. Naunyn-Schmiedeberg's Arch. Pharmacol. 294, 157–160 (1976). https://doi.org/10.1007/BF00507848
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DOI: https://doi.org/10.1007/BF00507848