Abstract
The developmental change of endogenous glutamate, as correlated to that of gamma-glutamyl transferase and other glutamate metabolizing enzymes such as phosphate activated glutaminase, glutamate dehydrogenase and aspartate, GABA and ornithine aminotransferases, has been investigated in cultured cerebral cortex interneurons and cerebellar granule cells. These cells are considered to be GABAergic and glutamatergic, respectively. Similar studies have also been performed in cerebral cortex and cerebellum in vivo. The developmental profiles of endogenous glutamate in cultured cerebral cortex interneurons and cerebellar granule cells corresponded rather closely with that of gamma-glutamyl transferase and not with other glutamate metabolizing enzymes. In cerebral cortex and cerebellum in vivo the developmental profiles of endogenous glutamate, gamma-glutamyl transferase and phosphate activated glutaminase corresponded with each other during the first 14 days in cerebellum, but this correspondence was less good in cerebral cortex. During the time period from 14 to 28 days post partum the endogenous glutamate concentration showed no close correspondence with any particular enzyme. It is suggested that gamma-glutamyltransferase regulates the endogenous glutamate concentration in culture neurons. The enzyme may also be important for regulation of endogenous glutamate in brain in vivo and particularly in cerebellum during the first 14 days post partum. Gamma-glutamyl transferase in cultured neurons and brain tissue in vivo appears to be devoid of maleate activated glutaminase.
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Abbreviations
- Asp-T:
-
aspartate aminotransferase (EC 2.6.1.1)
- GABA-T:
-
GABA aminotransferase (EC 2.6.1.19)
- GAD:
-
glutamate decarboxylase (EC 4.1.1.15)
- gamma-GT:
-
gamma-glutamyl transferase (gamma-glutamyl transpeptidase) (EC. 2.3.2.2)
- Glu:
-
glutamate
- GDH:
-
glutamate dehydrogenase (EC 1.4.1.3)
- GS:
-
glutamine synthetase (EC 6.3.1.2)
- MAG:
-
maleate activated glutaminase
- Orn-T:
-
ornithine aminotransferase (EC 2.6.1.13)
- PAG:
-
phosphate activated glutaminase (EC 3.5.1.1)
References
Albert, Z., Rzucidlo, Z., andStarzyk, H. 1970. Comparative biochemical and histochemical studies of the activity of gamma-glutamyl transpeptidase in the organs of fetuses, newborns and adult rats. Acta Histochem. 37:74–79.
Allison, R. D., andMeister, A. 1981. Evidence that transpeptidation is a significant function of gamma-glutamyl transpeptidase. J. Biol. Chem. 256:2988–2992.
Caspers, M. L., andDiglio, C. A. 1984. Expression of gamma-glutamyltranspeptidase in a transformed rat cerebral endothellial cell line. Biochim. Biophys. Acta 803:1–6.
The Committee on Enzymes of the Scandinavian Society for Clinical Chemistry and Clinical Physiology. 1976. Recommended method for the determination of gamma-glutamyltransferase in blood. Scand. J. Clin. Lab. Invest. 36:119–125.
Crook, R. B., Kasagami, H., andPrusiner, S. B. 1981. Culture and characterization of epithelial cells from bovine choroid plexus. J. Neurochem. 37:845–854.
Curthoys, N. P., andLowry, O. H. 1973. The distribution of glutaminase isoenzymes in the various structures of the nephron in normal, acidotic, and alkalotic rat kidney. J. Biol. Chem. 248:162–168.
Curthoys, N. P., andKuhlenschmidt, T. 1975. Phosphate-independent glutaminase from rat kidney. Partial purification and identity with gamma-glutamyltranspeptidase. J. Biol. Chem. 250:2099–2105.
Dass, P. O., andWu, M.-C. 1984. Role of gamma-GTP in glutamine uptake and metabolism in NRK. Fed. Proc. 43:1693.
Dichter, M. A. 1978. Rat cortical-neurons in cell culture—culture methods, cell morphology, electrophysiology and synapse formation. Brain Res. 149:279–293.
Drejer, J., Larsson, O. M., Kvamme, E., Svenneby, G., Hertz, L., andSchousboe, A. 1985. Ontogenetic development of glutamate metabolizing enzymes in culture cerebellar granule cells and in cerebellum in vivo. Neurochem. Res. 10:46–62.
Drejer, J., andSchousboe, A. 1984. Ornithine-δ-aminotransferase exhibits different kinetic properties in astrocytes, cerebral cortex interneurons, and cerebellar granule cells in primary culture. J. Neurochem. 42:1194–1197.
Grandgeorge, M., andMorélis, P. 1976. Purification partielle et étude de la gammaglutamyl transpeptidase des capillaires cérébraux de mouton. Biochimie 58:275–284.
Hertz, L., Yu, A., Svenneby, G., Kvamme, E., Fosmark, H., andSchousboe, A. 1980. Absence of preferential uptake of glutamine into neurons—an indication of a net transfer of TCA constituents from nerve endings to astrocytes? Neurosci. Lett. 16:103–109.
Hertz, L., Yu, A., Potter, R., Fischer, T., andSchousboe, A. 1983. Metabolic fluxes from glutamate and towards glutamate in neurons and astrocytes in primary cultures. Pages 327–342,in Hertz, L., Kvamme, E., McGeer, E. G., andSchousboe, A. (eds.), Glutamine, Glutamate and GABA in the Central Nervous System, Alan Liss, Inc., New York.
Kvamme, E. 1983. Glutamine. Pages 405–422,in Lajtha, A. (ed.), Handbook of Neurochemistry, 2nd ed., Vol. 3, Plenum Press, New York.
Kvamme, E. 1984. Enzymes of cerebral glutamine metabolism. Pages 32–48,in Häussinger, D., andSies, H. (eds.), Glutamine Metabolism in Mammalian Tissues, Springer Verlag, Berlin.
Kvamme, E., andLenda, K. 1981. Evidence for compartmentalization of glutamate in rat brain synaptosomes using the glutamate sensitivity of phosphate activated glutaminase as a functional test. Neurosci. Lett. 25:193–198.
Kvamme, E., andOlsen, B. E. 1981. Evidence for compartmentation of synaptosomal phosphate-activated glutaminase. J. Neurochem. 36:1916–1923.
Larsson, O. M., Drejer, J., Kvamme, E., Svenneby, G., Hertz, L., andSchousboe, A. 1985. Ontogenetic development of glutamate and GABA metabolizing enzymes in cultured cerebral cortex interneurons and in cerebral cortex in vivo. Int. J. Devl. Neurosci. 3:177–185.
Lisy, V., Stastný, F., Murphy, S., andHájková, B. 1983. Glutamate uptake into cerebral cortex slices is reduced in the presence of a gamma-glutamyl transpeptidase inhibitor. Experimentia 39:111.
McFarlane-Anderson, N., andAlleyne, G. A. O. 1979. Transport of glutamine by rat kidney brush-border membrane vesicles. Biochem. J. 182:295–300.
Meier, E., andSchousboe, A. 1982. Differences between GABA receptor binding to membranes from cerebellum during postnatal development and from cultured cerebellar granule cells. Devl. Neurosci. 5:546–553.
Messer, A. 1977. The maintenance and identification of mouse cellular granule cells in mono layer culture. Brain Res. 130:1–12.
Miller, S. P., Awasthi, Y. C., andSrivastava, S. K. 1976. Studies of human kidney gamma-glutamyl transpeptidase. Purification and structural, kinetic and immunological properties. J. Biol. Chem. 251:2271–2278.
Minn, A., andBesagni, D. 1983. Uptake ofl-glutamine into synaptosomes. Life Sci. 33:225–232.
Orlowski, M., andMeister, A. 1965. Isolation of gamma-glutamyl transpeptidase from hog kidney. J. Biol. Chem. 240:338–347.
Pajari, M. 1984. Properties of gamma-glutamyltransferase in developing rat brain. Int. J. Devl. Neurosci. 2:197–202.
Potashner, S. J. 1978. The spontaneous and electrically evoked release, from slices of guinea-pig cerebral cortex, of endogenous amino acids labelled via metabolism of d-[U-14C]glucose. J. Neurochem. 31:177–186.
Shank, R. P., andCampbell, G. LeM. 1983. Glutamate. Pages 381–404,in Lajtha, A. (ed.), Handbook of Neurochemistry, 2nd ed., Vol. 3, Plenum Press, New York.
Shine, H. D., Hertz, L., De Vellis, J., andHaber, B. 1981. A fluorometric assay for gamma-glutamyl transpeptidase: demonstration of enzymatic activity in cultured cells of neural origin. Neurochem. Res. 6:453–463.
Sikka, S. C., andKalra, V. K. 1980. Gamma-glutamyl transpeptidase mediated transport of amino acid in lecithin vesicles. J. Biol. Chem. 255:4399–4402.
Storm-Mathisen, J., Leknes, A. K., Bore, A. T., Vaaland, J. L., Edminson, P., Haug, F.-M. S., andOttersen, O. P. 1983. First visualization of glutamate and GABA in neurones by immunocytochemistry. Nature 301:517–520.
Tate, S. S. andMeister, A. 1974. Interaction of gamma-glutamyl transpeptidase with amino acids, dipeptides, and derivatives and analogs of glutathione. J. Biol. Chem. 249:7593–7602.
Tate, S. S., andMeister, A. 1975. Identity of maleate-stimulated glutaminase with gamma-glutamyl transpeptidase in rat kidney. J. Biol. Chem. 250:4619–4627.
Tate, S. S., andMeister, A. 1981. Gamma-glutamyl transpeptidase: catalytic, structural and functional aspects. Mol. Cell. Biochem. 39:357–368.
Wapnir, R. A., Mancusi, V. J., andGoldstein, L. A. 1982. Comparative ontogenesis of gamma-glutamyl transpeptidase in rat tissues. Experientia 38:647–648.
Wilkin, G. P., Balazs, R., Wilson, J. E., Cohen, J., andDutton, G. R. 1976. Preparation of cell bodies from the developing cerebellum. Structural and metabolic integrity of the isolated cells. Brain Res. 115:181–199.
Yu, A. C. H. andHertz, L. 1982. Uptake of glutamate, GABA, and glutamine into a predominantly GABAergic and predominantly glutamatergic nerve cell population in culture. J. Neurosci. Res. 7:23–35.
Yu, A. C. H., Fisher, T. E., Hertz, E., Tildon, J. T., Schousboe, A., andHertz, L. 1984. Metabolic fate of [14C]glutamine in mouse cerebral neurons in primary cultures. J. Neurosci. Res. 11:351–357.
Yu, A. C. H., Hertz, E., andHertz, L. 1984. Alterations in uptake and release rates for GABA, glutamate, and glutamine during biochemical maturation of highly purified cultures of cerebral cortical neurons, a GABAergic preparation. J. Neurochem. 42:951–960.
Zamenhof, S. 1957. Preparation and assay of desoxyribonucleic acid from animal tissue. Pages 696–704,in Colowick, S. P., andKaplan, N. O. (eds.), Methods in Enzymology, Vol. 3, Academic Press, London and New York.
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Kvamme, E., Schousboe, A., Hertz, L. et al. Developmental change of endogenous glutamate and gamma-glutamyl transferase in cultured cerebral cortical interneurons and cerebellar granule cells, and in mouse cerebral cortex and cerebellum in vivo. Neurochem Res 10, 993–1008 (1985). https://doi.org/10.1007/BF00964635
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DOI: https://doi.org/10.1007/BF00964635