Summary
The accumulation of GABA in the cerebellum and medulla oblongata-pons of rats has been studied after inhibition of GABA-T (EC 2.6.1.19) by different doses of AOAA. It was found that intraperitoneal (i.p.) injections of AOAA were, at least during the first hour after injection, much less effective than intravenous (i.v.) injections probably due to poor absorption i.p. After i.v. injection, AOAA caused a maximal accumulation of GABA in the cerebellum at a dose of 50 mg/kg. This maximal effect was virtually unchanged up to a dose of 150 mg/kg (the highest dose tested i.v.). If GAD (EC 4.1.1.15) was inhibited by 3-mercaptopropionic acid 30 min after AOAA (90 mg/kg i.v.) the GABA level was stable for at least another 30 min. The rate of GABA accumulation in the cerebellum during the first 15 min after AOAA (50–150 mg/kg i.v.) was 0.086 μmol/g/min and thereafter 0.034 μmol/g/min. It is concluded that AOAA in vivo in a wide dose range inhibits GABA-T almost 100% without affecting GAD to any great extent, and that the onset of action is rapid after i.v. but not after i.p. injection.
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Andén, N. E., Carlsson, A., Häggendal, J.: Adrenergic mechanisms. Ann. Rev. Pharmacol. 9, 119–133 (1969)
Baxter, C. F.: Some recent advances in studies of GABA metabolism and compartmentation. In: GABA in nervous system function (E. Roberts, T. N. Chase, D. B. Tower, eds.), pp. 61–88. New York: Raven Press 1976
Baxter, C. F., Roberts, E.: Elevation of γ-aminobutyric acid in brain: Selective inhibition of γ-aminobutyric-α-ketoglutarate transaminase. J. Biol. Chem. 236, 3287–3294 (1961)
Carlsson, A., Davis, J. N., Kehr, W., Lindqvist, M., Atack, C. V.: Simultaneous measurement of tyrosine and tryptophane hydroxylase activities in brain in vivo using an inhibitor of the aromatic amino acid decarboxylase. Naunyn-Schmiedeberg's Arch. Pharmacol. 275, 153–168 (1972)
Carmona, E., Gomes, C., Trolin, G.: Separation of GABA on small columns of Dowex 50W; combination with a method for separation of biogenic amines. Acta Pharmacol. Toxicol. (in press, 1980)
Collins, G. G. S.: GABA-2-oxoglutarate transaminase, glutamate decarboxylase and the half life of GABA in different areas of rat brain. Biochem. Pharmacol. 21, 2849–2858 (1972)
DaVanzo, J. P., Kang, R., Ruckard, R., Daugherty, M.: Inhibition of pyridoxal phosphokinase by aminooxy acetic acid. Biochem. Pharmacol. 15, 124–126 (1966)
Gomes, C., Trolin, G.: A simple and rapid method for the isolation of GABA. Resumos do VII Congresso Latinoamericano de Farmacologia, São Paulo. Abstr. 86, p. 86 (1978)
Heyden, J. A. M., Korf, J.: Regional levels of GABA in the brain: rapid semiautomatic assay and prevention of postmortem increase by 3-mercaptopropionic acid. J. Neurochem. 31, 197–203 (1978)
Jung, M. J., Lippert, B., Metcalf, B. W., Schechter, P. J., Böhlen, P., Sjoerdsma, A.: The effect of 4-amino hex-5-yonic acid (γ-acetylenic GABA, γ-ethynyl GABA) a catalytic inhibitor of GABA transaminase on brain GABA metabolism in vivo. J. Neurochem. 28, 717–723 (1977)
Karlsson, A., Fornum, F., Malthe-Sorenssen, D., Storm-Mathiesen, J.: Effect of the convulsive agent 3-mercaptopropionic acid on the levels of GABA, other aminoacids and glutamate decarboxylase in different regions of the rat brain. Biochem. Pharmacol. 23, 3053–3056 (1974)
Löscher, W., Frey, H.-H.: Aminooxyacetic acid: Correlation between biochemical effects, anticonvulsant action and toxicity in mice. Biochem. Pharmacol. 27, 103–108 (1978)
Neff, N. H., Tozer, T. N.: In vivo measurement of brain serotonine turnover. Adv. Pharmacol. 9, 119–133 (1968)
Perez de la Mora, M., Fuxe, K., Hökfelt, T., Ljungdahl, Å.: Effect of apomorphine on the GABA turnover in the DA cell group rich area of the mesencephalon. Evidence for involvement of an inhibitory GABAergic feedback control of the ascending DA neurons. Neurosci. Lett. 1, 109–114 (1975)
Peričić, D., Walters, J. R., Chase, T. N.: Effect of diazepam and pentobarbital on aminooxyacetic acid induced accumulation of GABA. J. Neurochem. 29, 839–846 (1977)
Peričić, D., Eng, N., Walters, J. R.: Postmortem and aminooxyacetic acid induced accumulation of GABA: Effect of gammabutyrolactone and picrotoxine. J. Neurochem. 30, 767–773 (1978)
Roberts, E., Simonsen, D. G.: Some properties of l-glutamic acid decarboxylase in mouse brain. Biochem. Pharmacol. 12, 113–134 (1963)
Rodriguez de Lores Arnaiz, G., Alberici de Canal, M., deRobertis, E.: Alteration of GABA system and Purkinje cells in rat cerebellum by the convulsant 3-mercaptopropionic acid. J. Neurochem. 19, 1379–1385 (1972)
Walters, J. R., Eng, N., Peričić, D., Miller, L. P.: Effects of aminooxyacetic acid and l-glutamic acid-γ-hydrazide on GABA metabolism in specific brain regions. J. Neurochem. 30, 759–766 (1978)
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Carmona, E., Gomes, C. & Trolin, G. Effect of aminooxyacetic acid (AOAA) on GABA levels in some parts of the rat brain. Naunyn-Schmiedeberg's Arch. Pharmacol. 312, 51–55 (1980). https://doi.org/10.1007/BF00502574
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DOI: https://doi.org/10.1007/BF00502574