Abstract
There exist differences between 12-day-old and adult rats in the onset of seizures induced by some inhibitors of glutamate decarboxylase (GAD). The aim of study was to investigate if there are differences between both groups in activities of rat brain alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the enzymes involved in glutamate metabolism, after the administration of 3-mercaptopropionic acid as specific GAD inhibitor or isoniazid as less specific general inhibitor of pyridoxal enzymes. Activities of both aminotransferases in a supernatant 20,000 g of the whole brain (containing predominantly cytosolic isoforms of enzymes) were increased at the beginning of 3-mercaptopropionic acid-induced generalized tonic-clonic seizures. At isoniazid-induced generalized tonic-clonic seizures, a significant increase in both enzyme activities was observed in adult rat brain. In the 12-day-old rat brain, ALT and AST activities reached about 40% and about 50–60% of adult control levels, respectively. In in vitro experiments, no influence of 3-mercaptopropionic acid on transaminase activities was found and an inhibitory effect of isoniazid on the enzymes was confirmed. Increased aminotransferase activities might participate in the enhanced synthesis of excitatory amino acid neurotransmitters in the nervous system, which may take a part in the initiation of epileptic seizures. Alternatively, the increased AST activity may be connected with an increased transport of NADH from the cytosol to mitochondria, while the increased ALT activity would represent the transformation of pyruvate to alanine as a consequence of increased glycolysis.
Similar content being viewed by others
REFERENCES
Meldrum, B. S. 1994. The role of glutamate in epilepsy and other CNS disorders. Neurology 44:S14–S23.
Urbanska, E. M., Czuczwar, S. J., Kleinrok, Z., and Turski, W. A. 1998. Excitatory amino acids in epilepsy. Restorat. Neurolog. Neurosci. 13:25–39.
Benuck, M. and Lajtha, A. 1975. Aminotransferase activity in brain. Int. Rev. Neurobiol. 17:85–129.
Kugler, P. 1993. Enzymes involved in glutamatergic and GABAergic neurotransmission. Int. Rev. Cytolog. 147:285–336.
Palaiologos, G., Hertz, L., and Schousboe, A. 1988. Evidence that aspartate aminotransferase activity and ketodicarboxylate carrier function are essential for biosynthesis of transmitter glutamate. J. Neurochem. 51:317–320.
Palaiologos, G., Hertz, L., and Schousboe, A. 1989. Role of aspartate aminotransferase and mitochondrial dicarboxylate transport for release of endogenously and exogenously supplied neurotransmitter in glutamatergic neurons. Neurochem. Res. 14:359–366.
Kubo, T., Kihara, M., and Misu, Y. 1990. Electrical stimulationevoked release of endogenous aspartate from rat medulla oblongata slices. Naunyn-Schmiedeberg's Arch. Pharmacol. 341:221–224.
Fonnum, F. 1993. Regulation of the synthesis of the transmitter glutamate pool. Prog. Biophys. Mol. Biol. 60:47–57.
Peng, L., Schousboe, A., and Hertz, L. 1991. Utilization of alpha-ketoglutarate as a precursor for transmitter glutamate in cultured cerebellar granule cells. Neurochem. Res. 16:29–34.
Rodríguez de Lores Arnáiz, G., Alberici de Canal, M., and de Robertis, E. 1972. Alteration of GABA system and Purkinje cells in rat cerebellum by the convulsant 3-mercaptopropionic acid. J. Neurochem. 19:1379–1385.
Rodríguez de Lores Arnáiz, G., Alberici de Canal, M., Robiolo, B., and Mistrorigo de Pacheco, M. 1973. The effect of the convulsant 3-mercaptopropionic acid on enzymes of the gammaaminobutyrate system in the rat cerebral cortex. J. Neurochem. 21:615–623.
Mareš, P., Kubová, H., Zouhar, A., Folbergrová, J., Koryntová, H., and Staňková, L. 1993. Motor and electrocorticographic epileptic activity induced by 3-mercaptopropionic acid in immature rats. Epilepsy Res. 16:11–18.
Mareš, P. and Trojan, S. 1991. Ontogenetic development of isonicotinehydrazide-induced seizures in rats. Brain Dev. 13:121–125.
Netopilová, M., Dršata, J., Kubová, H., and Mareš, P. 1995. Differences between immature and adult rats in brain glutamate decarboxylase inhibition by 3-mercaptopropionic acid. Epilepsy Res. 20:179–184.
Netopilová, M. 1997. Activity of glutamate decarboxylase in rat brain during experimental epileptic seizures in ontogenesis. Doctoral thesis, Charles University, Hradec Králové. pp. 141.
Bergmeyer, H. U. and Bernt, E. 1974. Glutamat-Oxalacetat-Transaminase. UV-Test, manualle Methode. Pages 769–775, in Bergmeyer, H. U. (ed.), Methoden der enzymatischen Analyse, Band I, Verlag Chemie, Weinheim.
Bergmeyer, H. U. and Bernt, E. 1974. Glutamat-Pyruvat-Transaminase. UV-Test, manualle Methode. Pages 785–791, in Bergmeyer, H. U. (ed.), Methoden der enzymatischen Analyse, Band I, Verlag Chemie, Weinheim.
Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193:265–275.
Waksman, A. and Rendon, A. 1968. Postnatal development of aspartate aminotransferase isozymes in different organs of the rat. Arch. Biochem. Biophys. 123:201–208.
Amore, G. and Bonavita, V. 1965. Aspartate aminotransferase in the brain of the developing rat. Life Sci. 4:2417–2424.
Orlický, J., Ruš čák, M., Ruš čáková, D., and Hager, H. 1979. Two forms of alanine aminotransferase in rat brain during ontogeny. J. Neurochem. 32:1551–1558.
Jenkins, W. T., Orlowski, S., and Sizer, I. W. 1959. Glutamic aspartic transaminase. III. Inhibition by isoniazid. J. Biol. Chem. 234:2657–2660.
Alioto, M. R. and Ayala, M. 1960. Altre ricerche sulla inibizione esercitata dall'idrazide della'ac. isonicotinico (INI) sull'-alanina-glutammico transaminasi. Boll. Soc. Ital. Biol. Sper. 36:327–329.
Pirrelli, A. 1961. Rapporti tra glutammico-ossalacetico e glutammico-piruvico transaminasi epatica e cerebrale di ratto e idrazide dell'acido isonicotinico. Accad. Pugliese Sci. Atti. Relaz. 19:133–143.
Meldrum, B. S. 1975. Epilepsy and γ-aminobutyric acid-mediated inhibition. Int. Rev. Neurobiol. 17:1–36.
Woodbury, D. M. 1980. Convulsant drugs: Mechanisms of action. Pages 249–303, in Glaser, G. H., Penry, J. K., and Woodbury, D. M. (eds.), Antiepileptic drugs: Mechanisms of action, Raven Press, New York.
Stankewicz, M. J., Cheng, S., and Martinez-Carrion, M. 1971. Mitochondrial glutamate aspartate transaminase. Differential action of thiol reagents with the supernatant enzyme. Biochemistry 10:2877–2884.
Bonasera, N., Smorto, M., and Bonavita, V. 1967. Isoniazid seizures in the developing rat and the content of pyridoxal 5-phosphate in the brain. Brain Res. 4:383–386.
Lamar, C. Jr. 1970. Mercaptopropionic acid: A convulsant that inhibits glutamate decarboxylase. J. Neurochem. 17:165–170.
Tunnicliff, G. 1990. Action of inhibitors on brain glutamate decarboxylase. Int. J. Biochem. 22:1235–1241.
Killam, K. F. and Bain, J. A. 1957. Convulsant hydrazides I: In vitro and in vivo inhibition of vitamin B6 enzymes by convulsant hydrazides. J. Pharmacol. Exptl. Therap. 119:255–262.
Netopilová, M., Dršata, J., Haugvicová, R., Kubová, H., and Mares¡, P. 1997. Inhibition of glutamate decarboxylase activity by 3-mercaptopropionic acid has different time course in the immature and adult rat brains. Neurosci. Lett. 226:68–70.
Najlerahim, A., Harrison, P. J., Barton, A. J. L., Heffernan, J., and Pearson, R. C. A. 1990. Distribution of messenger RNAs encoding the enzymes glutaminase, aspartate aminotransferase and glutamic acid decarboxylase in rat brain. Mol. Brain Res. 7:317–333.
Howse, D. C. and Duffy, T. E. 1975. Control of the redox state of the pyridine nucleotides in the rat cerebral cortex. Effect of electroshock-induced seizures. J. Neurochem. 24:935–940.
Ereci´nska, M., Nelson, D., Nissim, I., Daikhin, Y., and Yudkoff, M. 1994. Cerebral alanine transport and alanine aminotransferase reaction: Alanine as a source of neuronal glutamate. J. Neurochem. 62:1953–1964.
Griffin, J. L., Rae, C., Dixon, R. M., Radda, G. K., and Matthews, P. M. 1998. Excitatory amino acid synthesis in hypoxic brain slices: Does alanine act as a substrate for glutamate production in hypoxia? J. Neurochem. 71:2477–2486.
Cooper, A. J. L. and Meister, A. 1985. Metabolic significance of transamination. Pages 534–563, in Christen, P. and Metzler, D. E. (eds.), Transaminases, John Wiley and Sons, New York.
Lia, M., Barouki, R., and Waelsch, S. G. 1995. Chromosomal deletions around the albino locus in the mouse cause loss of hormone-inducible expression of the unlinked structural gene encoding cytosolic aspartate aminotransferase. Proc. Natl. Acad. Sci. USA 92:788–790.
Pavé-Preux, M., Ferry, N., Bouguet, J., Hanoune, J., and Barouki, R. 1988. Nucleotide sequence and glucocorticoid regulation of the mRNAs for the isoenzymes of rat aspartate aminotransferase. J. Biol. Chem. 263:17459–17466.
Rosen, F., Roberts, N. R., Budnick, L. E., and Nichol, C. A. 1958. An enzymic basis for the gluconeogenic action of hydrocortisone. Science 127:287–288.
Patnaik, S. K. 1990. Differential effects of hydrocortisone on alanine aminotransferase isoenzymes of the cerebral hemisperes and cerebellum of rats during growth, development, and senescence. Biochem. Int. 21:175–184.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Netopilová, M., Haugvicová, R., Kubová, H. et al. Influence of Convulsants on Rat Brain Activities of Alanine Aminotransferase and Aspartate Aminotransferase. Neurochem Res 26, 1285–1291 (2001). https://doi.org/10.1023/A:1014386416109
Issue Date:
DOI: https://doi.org/10.1023/A:1014386416109