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Taurine and GABA release from mouse cerebral cortex slices: Effects of structural analogues and drugs

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The effects of structural analogues, excitatory amino acids and certain drugs on spontaneous and potassium-stimulated exogenous taurine and GABA release were investigated in mouse cerebral cortex slices using a superfusion system. Spontaneous efflux of both amino acids was rather slow but could be enhanced by their uptake inhibitors. Taurine efflux was facilitated by exogenous taurine, hypotaurine, β-alanine and GABA, whereas GABA, nipecotic acid and homotaurine effectively enhanced GABA release. The stimulatory potency of the analogues closely corresponded to their ability to inhibit taurine and GABA uptake, respectively, indicating that these efflux processes could be mediated by the carriers operating outwards. Glutamate induced GABA release, whereas taurine efflux was potentiated by aspartate, glutamate, cysteate, homocysteate and kainate. The centrally acting drugs, including GABA agonists and antagonists, as well as the proposed taurine antagonist TAG (6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine-1,1-dioxide), had no marked effects on spontaneous taurine and GABA release. Potassium ions stimulated dosedependently both taurine and GABA release from the slices, the responses of taurine being strikingly slow but sustained. Exogenous GABA and nipecotic acid accelerated the potassium-stimulated GABA release, whereas picrotoxin and bicuculline were ineffective. The potassium-stimulated taurine release was unaltered or suppressed by exogenous taurine and analogues, differing in this respect from GABA release. The apparent magnitude of the depolarization-induced GABA release is thus influenced by the function of membrane transport sites, but the same conclusion cannot be drawn with regard to taurine. Haloperidol and imipramine were able to affect the evoked release of both taurine and GABA.

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References

  1. Levi, G. 1984, Release of putative transmitter amino acids. Pages 463–509in Lajtha, A. (ed), Handbook of Neurochemistry, Vol. 6, 2nd edn., Plenum Press, New York.

    Google Scholar 

  2. Oja, S. S., and Kontro, P. 1983. Taurine. Pages 501–533, in Lajtha, A. (ed.), Handbook of Neurochemistry, Vol. 3, 2nd edn, Plenum Press, New York.

    Google Scholar 

  3. Martin, D. L., and Shain, W. 1979. High-affinity transport of taurine and β-alanine and low-affinity transport of γ-aminobutyric acid by a single transport system in cultured glioma cells. J. Biol. Chem. 254:7076–7084.

    Google Scholar 

  4. Kontro, P., and Oja, S. S. 1981. Hypotaurine transport in brain slices: comparison with taurine and GABA. Neurochem. Res. 6:1179–1191.

    Google Scholar 

  5. Kontro, P. 1982. Effects of cations on taurine, hypotaurine, and GABA uptake in mouse brain slices. Neurochem. Res. 7:1391–1401.

    Google Scholar 

  6. Holopainen, I., Kontro, P., Frey, H. J., and Oja, S. S. 1983. Taurine, hypotaurine, and GABA uptake by cultured neuroblastoma cells. J. Neurosci. Res. 10:83–92.

    Google Scholar 

  7. Holopainen, I., and Kontro, P. 1986. High-affinity uptake of taurine and β-alanine in primary cultures of rat astrocytes. Neurochem. Res. 11:207–215.

    Google Scholar 

  8. Kontro, P., and Oja, S. S. 1983. Mutual interactions in the transport of taurine, hypotaurine and GABA in brain slices. Neurochem. Res. 8:1377–1387.

    Google Scholar 

  9. Huxtable, R. J., Laird, H. E. II., and Lippincott, S. E. 1979. The transport of taurine in the heart and the rapid depletion of tissue taurine content by guanidinoethyl sulfonate. J. Pharmacol. Exp. Ther. 211:465–471.

    Google Scholar 

  10. Korpi, E. R., and Oja, S. S. 1984. Comparison of two superfusion systems for study of neurotransmitter release from rat cerebral cortex slices. J. Neurochem. 43:236–242.

    Google Scholar 

  11. Oja, S. S. and Kontro, P. 1987. Cation effects on taurine release from brain slices: comparison to GABA. J. Neurosci. Res., in press.

  12. Korpi, E. R., and Oja, S. S. 1979. Efflux of phenylalanine from rat cerebral cortex slices as influenced by extra- and intracellular amino acids. J. Neurochem. 32:789–796.

    Google Scholar 

  13. Snedecor, G. W. 1956. Statistical Methods. 5th edn. Iowa State College Press, Ames.

    Google Scholar 

  14. Olsen, R. W., Lamar, E. E., and Bayless, J. D. 1977. Calcium induced release of γ-aminobutyric acid from synaptosomes: effects of tranquilizer drugs. J. Neurochem. 28:299–305.

    Google Scholar 

  15. Brennan, M. J. W., and Cantrill, R. C. 1978. The effect of DABA and β-alanine on the efflux of [3H]GABA from preloaded rat brain synaptosomes. J. Neurochem. 31:1339–1341.

    Google Scholar 

  16. Snodgrass, S. R. 1978. Use of3H-muscimol for GABA receptor studies. Nature (Lond.) 273:392–394.

    Google Scholar 

  17. Do Nascimento, J. L. M., and Mello, F. G. 1985. Induced release of γ-aminobutyric acid by a carrier-mediated, highaffinity uptake ofl-glutamate in cultured chick retina cells. J. Neurochem. 45:1820–1827.

    Google Scholar 

  18. Kontro, P. 1979. Components of taurine efflux in rat brain synaptosomes. Neuroscience 4:1745–1749.

    Google Scholar 

  19. Kontro, P. 1984. Comparison of taurine, hypotaurine and β-alanine uptake in brain synaptosomal preparations from developing and adult mouse. Int. J. Dev. Neurosci. 2:465–470.

    Google Scholar 

  20. Johnston, G. A. R., Stephanson, A. L., and Twitchin, B. 1976. Uptake and release of nipecotic acid by rat brain slices. J. Neurochem. 26:83–87.

    Google Scholar 

  21. Early, S. L., Michaelis, E. K., and Mertes, M. P. 1981. Pharmacological specificity of synaptosomal and synaptic membrane γ-aminobutyric acid (GABA) transport processes. Biochem. Pharmacol. 30:1105–1113.

    Google Scholar 

  22. Levi, G., Banay-Schwartz, M., and Raiteri, M. 1978. Uptake, exchange and release of GABA in isolated nerve endings. Pages 327–350 in Fonnum, F. (ed.) Amino Acids as Chemical Transmitters, Plenum Press, New York.

    Google Scholar 

  23. Lerma, J., Herranz, A. S., Herreras, O., Mu noz, D., Solis, J. M., Del Rio, R. M., and Delgado, J. M. R. 1985. γ-Aminobutyric acid greatly increases the in vivo extracellular taurine in the rat hippocampus. J. Neurochem. 44:983–986.

    Google Scholar 

  24. Szerb, J. C. 1982. Effect of nipecotic acid, a γ-aminobutyric acid transport inhibitor, on the turnover and release of γ-aminobutyric acid in rat cortical slices. J. Neurochem. 39:850–858.

    Google Scholar 

  25. Jaffe, E. H., Hernandez, N., and Holder, L. G. 1984. Study of the mechanism of release of [3H]GABA from a teleost retina in vitro. J. Neurochem. 43:1226–1235.

    Google Scholar 

  26. Lerma, J., Herreras, O., Herranz, A. S., Mu oz, D., and Del Rio, R. M. 1984. In vivo effects of nipecotic acid on levels of extracellular GABA and taurine, and hippocampal excitability. Neuropharmacology 23:595–598.

    Google Scholar 

  27. Kontro, P. 1983. β-Alanine uptake by mouse brain slices. Neuroscience 8:153–159.

    Google Scholar 

  28. Hammerstad, J. P., and Lytle, C. R. 1976. Release of [3H]GABA from rat cortical slices: neuronal vs. glial origin. J. Neurochem. 27:399–403.

    Google Scholar 

  29. Hammerstad, J. P., Cawthon, M. L., and Lytle, C. R. 1979. Release of [3H]GABA from in vitro preparations: comparison of the effect of DABA and β-alanine on the K+ and protoveratrine stimulated release of [3H]GABA from brain slices and synaptosomes. J. Neurochem. 32:195–202.

    Google Scholar 

  30. Borg, J., Balcar, V. J., Mark, J., and Mandel, P. 1979. Characterization of taurine uptake by neuronal and glial cells in culture. J. Neurochem. 32:1801–1805.

    Google Scholar 

  31. Moran, J., and Pasantes-Morales, H. 1983. Effects of excitatory amino acids, and of their agonists and antagonists on the release of neurotransmitters from the chick retina. J. Neurosci. Res. 10:261–271.

    Google Scholar 

  32. Kontro, P., and Oja, S. S. 1984. Effects of 2-guanidinoethanesulphonic acid, convulsant and anticonvulsant drugs and amino acids on taurine uptake in mouse brain. Acta Univ. Tamper. [B] 21:30–36.

    Google Scholar 

  33. Mori, A., Katayama, Y., Yokoi, I., and Matsumoto, M. 1981. Inhibition of taurocyamine (guanidinotaurine)-induced seizures by taurine. Pages 41–48 in Schaffer, S. W., Baskin, S. I., and Kocsis, J. J. (eds) The Effects of Taurine on Excitable Tissues, Spectrum Press, Philadelphia.

    Google Scholar 

  34. Baba, A., Yamamoto, T., Morimoto, H., Matsuda, T., and Iwata, H. 1984. Release of [3H]γ-aminobutyric acid by taurocyamine in rat brain slices. Jap. J. Pharmacol. 35:465–467.

    Google Scholar 

  35. Ferkany, J. W., and Coyle, J. T. 1983. Kainic acid selectively stimulates the release of endogenous excitatory acidic amino acids. J. Pharmacol. Exp. Ther. 225:399–406.

    Google Scholar 

  36. Poli, A., Contestabile, A., Migani, P., Rossi, L., Rondelli, C., Virgili, M., Bissoli R., and Barnabei, O. 1985. Kainic acid differentially affects the synaptosomal release of endogenous and exogenous amino acid neurotransmitters. J. Neurochem. 45:1677–1686.

    Google Scholar 

  37. Kato, S., Negishi, K., and Tsunenobu, T. 1985. Dopamine inhibits calcium-independent γ-[3H]aminobutyric acid relase induced by kainate and high K+ in the fish retina. J. Neurochem. 44:893–899.

    Google Scholar 

  38. Lehmann, A., Isacsson, H., and Hamberger, A. 1983. Effects of in vivo administration of kainic acid on the extracellular amino acid pool in the rabbit hippocampus. 40:1314–1320.

  39. Lehmann, A., Hagberg, H., Jacobson, J., and Hamberger, A. 1985. Effects of stacus epilepticus on extracellular amino acids in the hippocampus. Brain Res. 359:147–151.

    Google Scholar 

  40. Yarbrough, G. G., Singh, D. K., and Taylor, D. A. 1981. Neuropharmacological characterization of a taurine antagonist. J. Pharmacol. Exp. Ther. 219:604–613.

    Google Scholar 

  41. Korpi, E. R., Kontro, P., Nieminen, K., Marnela, K.-M., and Oja, S. S. 1981. Spontaneous and depolarization-induced efflux of hypotaurine from mouse cerebral cortex slices: comparison with taurine and GABA. Life Sci. 29:811–816.

    Google Scholar 

  42. Girault, J. A., Barbeito, L., Scampinato, U., Gozlan, H., Glowinski, J., and Besson, M.-J. 1986. In vivo release of endogenous amino acids from the rat striatum: further evidence for a role of glutamate and aspartate in corticostriatal neurotransmission. J. Neurochem. 47:98–106.

    Google Scholar 

  43. Lehmann, A., Sandberg, M., and Huxtable, R. J. 1986. In vivo release of neuroactive amines and amino acids from the hippocampus of seizure-resistant and seizure-susceptible rats. Neurochem. Int. 8:513–520.

    Google Scholar 

  44. Smith, L. F. P., and Pycock, C. J. 1982. Potassium-stimulated release of radiolabelled taurine and glycine from the isolated rat retina. J. Neurochem. 39:653–658.

    Google Scholar 

  45. Kalsner, S. 1985. Is there feedback regulation of neurotransmitter release by autoreceptors? Biochem. Pharmacol. 34:4085–4097.

    Google Scholar 

  46. Brennan, M. J. W., Cantrill, R. C., Oldfield, M., and Krogsgaard-Larsen, P. 1980. Inhibition of γ-aminobutyric acid release by γ-aminobutyric acid agonist drugs. Pharmacology of the γ-aminobutyric acid autoreceptor. Mol. Pharmacol. 19:27–30.

    Google Scholar 

  47. Arbilla, S., Kamal, L., and Langer, S. Z. 1979. Presynaptic GABA autoreceptors on GABAergic nerve endings of the rat substantia nigra. Eur. J. Pharmacol. 57:211–217.

    Google Scholar 

  48. Collins, G. G. S. 1980. Release of endogenous amino acid neurotransmitter candidates from rat olfactory cortex slices: possible regulatory mechanisms and the effects of pentobarbitone. Brain Res. 190:517–528.

    Google Scholar 

  49. Namima, M., Okamoto, K., and Sakai, Y. 1983. Modulatory action of taurine on the release of GABA in cerebellar slices of the guinea pig. J. Neurochem. 40:1–9.

    Google Scholar 

  50. Leach, M. J. 1979. Effect of taurine on release of3H-GABA by depolarizing stimuli from superfused slices of rat brain cerebral cortex in vitro. J. Pharm. Pharmacol. 31:533–535.

    Google Scholar 

  51. Kontro, P., and Oja, S. S. 1985. Properties of sodium-independent taurine binding to brain synaptic membranes. Pages 249–259in Oja, S. S. Ahtee, L., Kontro, P., and Paasonen, M. K. (eds.) Taurine: Biological Actions and Clinical Perspectives, Alan R. Liss, New York.

    Google Scholar 

  52. Johnston, G. A. R., and Mitchell, J. F. 1971. Effect of bicuculline, metrazol, picrotoxin and strychnine on the release of [3H]GABA from rat brain slices. J. Neurochem. 18:2441–2446.

    Google Scholar 

  53. Tappaz, M., and Pacheco, H. 1973. Effects of convulsant and anticovvulsant drugs on the spontaneous and induced release of GABA14C from cortex slices of rat brain. J. Pharmacol. (Paris) 4:433–452.

    Google Scholar 

  54. Olsen, R. W., Ticku, M. K., Van Ness, P. C., and Greenlee, D. 1978. Effects of drugs on γ-aminobutyric acid receptors, uptake, release and synthesis in vitro. Brain Res. 139:277–294.

    Google Scholar 

  55. Korf, J., and Venema, K. 1983. Desmethylimipramine enhances the release of endogenous GABA and other neurotransmitter amino acids from the rat thalamus. J. Neurochem. 40:946–950.

    Google Scholar 

  56. Harris, M., Hopkin, J. M., and Neal, M. J. 1973. Effect of centrally acting drugs on the uptake of γ-aminobutyric acid (GABA) by slices of rat cerebral cortex. Br. J. Pharmacol. 47:229–239.

    Google Scholar 

  57. Schmid, R., Sieghart, W., and Karobath, M. 1975. Taurine uptake in synaptosomal fractions of rat cerebral cortex. J. Neurochem. 25:5–9.

    Google Scholar 

  58. Schousboe, A., Fosmark, H., and Svenneby, G. 1976. Taurine uptake in astrocytes cultured from dissociated brain hemispheres. Brain Res. 116:158–164.

    Google Scholar 

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Kontro, P., Oja, S.S. Taurine and GABA release from mouse cerebral cortex slices: Effects of structural analogues and drugs. Neurochem Res 12, 475–482 (1987). https://doi.org/10.1007/BF00972301

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