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The in vivo inactivation of GABA and other inhibitory amino acids in the cat nervous system

Experimental Brain Research volume 25, pages 413–428 (1976)Cite this article

Summary

In cats anaesthetised with pentobarbitone, the effect of inhibitors of the in vitro cellular uptake of GABA were tested on the responses of single central neurones to GABA and other depressant amino acids. (+)- And (-)-nipecotic acid, (+)-2,4-diaminobutyric acid (DABA) and 2,2-dimethyl-β-alanine, enhanced the action of GABA on spinal, cerebellar and cerebral cortical neurones.

In the spinal cord DABA, and to a less extent (-)-nipecotic acid, enhanced the action of β-alanine, whereas the actions of glycine and taurine were unaffected by DABA and reduced by (-)-nipecotic acid. In the cerebellum and cerebral cortex, these two substances enhanced the action of GABA, usually to a greater extent than that of β-alanine and taurine, although this specificity was not marked.

The GABA-mediated basket cell inhibition of Purkinje cells in the cerebellum was unaffected by DABA and (-)-nipecotic acid, and neither substance appears suitable for determining the role of uptake processes in the inactivation of synaptically released GABA.

Quantitatively these in vivo results agree more closely with recent in vitro uptake studies in cat tissue than the previously published data on rat cerebral cortex and dorsal root ganglia, and the observations provide further evidence for the importance of cellular uptake in maintaining low extraneuronal concentrations of inhibitory amino acid transmitters.

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References

  • Baxter, C.F., Roberts, E.: The γ-aminobutyric acid-α-ketoglutaric acid transaminase. J. biol. Chem. 233, 1135–1139 (1958)

    Google Scholar 

  • Crawford, J.M., Curtis, D.R.: The excitation and depression of mammalian cortical neurones by amino acids. Brit. J. Pharmacol. 23, 313–329 (1964)

    Google Scholar 

  • Crawford, J.M., Curtis, D.R., Voorhoeve, P.E., Wilson, V.J.: Acetylcholine sensitivity of cerebellar neurones in the cat. J. Physiol. (Lond.) 186, 139–165 (1966)

    Google Scholar 

  • Curtis, D.R., Duggan, A.W., Felix, D., Johnston, G.A.R.: Bicuculline, an antagonist of GABA and synaptic inhibition in the spinal cord. Brain Res. 32, 69–96 (1971a)

    Google Scholar 

  • Curtis, D.R., Duggan, A.W., Johnston, G.A.R.: The inactivation of extracellularly administered amino acids in the feline spinal cord. Exp. Brain Res. 10, 447–462 (1970)

    Google Scholar 

  • Curtis, D.R., Duggan, A.W., Johnston, G.A.R.: The specificity of strychnine as a glycine antagonist in the mammalian spinal cord. Exp. Brain Res. 12, 547–565 (1971b)

    Google Scholar 

  • Curtis, D.R., Felix, D.: The effect of bicuculline upon synaptic inhibition in the cerebral and cerebellar cortices of the cat. Brain Res. 34, 301–321 (1971)

    Google Scholar 

  • Curtis, D.R., Hösli, L., Johnston, G.A.R.: A pharmacological study of the depression of spinal neurones by glycine and related amino acids. Exp. Brain Res. 6, 1–18 (1968)

    Google Scholar 

  • Curtis, D.R., Johnston, G.A.R.: Amino acid transmitters in the mammalian central nervous system. Ergebn. Physiol. 69, 97–188 (1974)

    Google Scholar 

  • Curtis, D.R., Watkins, J.C.: The excitation and depression of spinal neurones by structurally related amino acids. J. Neurochem. 6, 117–141 (1960)

    Google Scholar 

  • Game, C.J.A., Lodge, D.: The pharmacology of the inhibition of dorsal horn neurones by impulses in myelinated cutaneous afferents in the cat. Exp. Brain Res. 23, 75–84 (1975)

    Google Scholar 

  • Iversen, L.L., Johnston, G.A.R.: GABA uptake in rat central nervous system: comparison of uptake in slices and homogenates and the effects of some inhibitors. J. Neurochem. 18, 1939–1950 (1971)

    Google Scholar 

  • Iversen, L.L., Kelly, J.S.: Uptake and metabolism of γ-aminobutyric acid by neurones and glial cells. Biochem. Pharmacol. 24, 933–938 (1975)

    Google Scholar 

  • Johnston, G.A.R., Iversen, L.L.: Glycine uptake in rat central nervous system slices and homogenates: evidence for different uptake systems in spinal cord and cerebral cortex. J. Neurochem. 18, 1951–1961 (1971)

    Google Scholar 

  • Johnston, G.A.R., Krogsgaard-Larsen, P., Stephanson, A.L., Twitchin, B.: Inhibition of the uptake of GABA and related ammo acids in rat brain slices by the optical isomers of nipecotic acid. J. Neurochem. 26, 1029–1033 (1976a)

    Google Scholar 

  • Johnston, G.A.R., Stephanson, A.L.: Inhibitors of the glial uptake of β-alanine in rat brain slices. Brain Res. 102, 374–378 (1976)

    Google Scholar 

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

    Google Scholar 

  • Kelly, J.S., Dick, F., Schon, F.: The autoradiographic localization of the GABA-releasing nerve terminals in cerebellar glomeruli. Brain Res. 85, 255–259 (1975)

    Google Scholar 

  • Krnjević, K.: Chemical nature of synaptic transmission in vertebrates. Physiol. Rev. 54, 418–540 (1974)

    Google Scholar 

  • Krogsgaard-Larsen, P., Johnston, G.A.R.: Inhibition of GABA uptake in rat brain slices by nipecotic acid, various isoxazoles and related compounds. J. Neurochem. 25, 797–802 (1975)

    Google Scholar 

  • Krogsgaard-Larsen, P., Johnston, G.A.R., Curtis, D.R., Game, C.J.A., McCulloch, R.M.: Structure and biological activity of a series of conformationally restricted analogues of GABA. J. Neurochem. 25, 803–809 (1975)

    Google Scholar 

  • Lasher, R.S.: Uptake of GABA by neuronal and nonneuronal cells in dispersed cell cultures of postnatal rat cerebellum. J. Neurobiol. 6, 597–608 (1975)

    Google Scholar 

  • Ljungdahl, Å., Hökfelt, T.: Autoradiographic uptake patterns of [3H]GABA and [3H]glycine in central nervous tissues with special reference to the cat spinal cord. Brain Res. 62, 587–595 (1973)

    Google Scholar 

  • Schon, F., Iversen, L.L.: The use of autoradiographic techniques for the identification and mapping of transmitter-specific neurones in the brain. Life Sci. 15, 157–175 (1974)

    Google Scholar 

  • Schon, F., Kelly, J.S.: The characterisation of [3H]GABA uptake into the satellite glial cells of rat sensory ganglia. Brain Res. 66, 289–300 (1974)

    Google Scholar 

  • Schon, F., Kelly, J.S.: Selective uptake of [3H]β-alanine by glia: association with the glial uptake system for GABA. Brain Res. 86, 243–257 (1975)

    Google Scholar 

  • Simon, J.R., Martin, D.L.: The effects of L-2,4-diaminobutyric acid on the uptake of gammaaminobutyric acid by a synaptosomal fraction from rat brain. Arch. Biochem. 157, 348–355 (1973)

    Google Scholar 

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Affiliations

  1. Department of Pharmacology, The Australian National University, P.O. Box 334, 2601, Canberra City, A.C.T., Australia

    D. R. Curtis, C. J. A. Game & D. Lodge

Authors
  1. D. R. Curtis
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  2. C. J. A. Game
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  3. D. Lodge
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Curtis, D.R., Game, C.J.A. & Lodge, D. The in vivo inactivation of GABA and other inhibitory amino acids in the cat nervous system. Exp Brain Res 25, 413–428 (1976). https://doi.org/10.1007/BF00241731

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  • DOI: https://doi.org/10.1007/BF00241731

Key words

  • Amino acid inactivation
  • GABA
  • Nipecotic acid
  • Diaminobutyric acid
  • β-Alanine