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A carrier for GABA uptake exists on noradrenaline nerve endings in selective rat brain areas but not on serotonin terminals

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Summary

γ-Aminobutyric acid (GABA) increased in a concentration-dependent way (3–300ΜM) the basal release of tritium from rat cerebral cortex and hippocampus synaptosomes, prelabelled with3H-noradrenaline (3H-NA); however, GABA was ineffective on hypothalamic nerve endings. The effect displayed by low concentrations (<10ΜM) of GABA was largely bicuculline-sensitive. Muscimol mimicked GABA, while (−)baclofen was inactive.

The releasing effects produced by concentrations of GABA higher than 10ΜM were largely prevented by SK&F89976A, SK&F 100330A and SK&F 100561, three novel GABA uptake inhibitors. When present together, GABA uptake blocker and bicuculline counteracted entirely the GABA effects. The basal release of3H-5-hydroxytryptamine (3H-5-HT) in synaptosomes from various CNS regions was not affected by GABA. In conclusion: GABA can enhance3H-NA release not only through GABA-A receptors but also by penetrating into NA terminals through a GABA uptake system. This implies coexistence of carriers for NA and GABA uptake on a same nerve terminal. The carrier coexistence occurs in selective CNS areas. The phenomenon appears to be transmitter-selective.

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References

  • Arbilla S, Langer SZ (1979) Facilitation by GABA of the potassium-evoked release of3H-noradrenaline from the rat occipital cortex. Naunyn Schmiedebergs Arch Pharmacol 306: 161–168

    PubMed  Google Scholar 

  • Bonanno G, Raiteri M (1986) On the presence of a GABA uptake system on cholinergic terminals of rat hippocampus: evidence for neuronal coxistence of acetylcholine and GABA? J Pharmacol Exp Ther (in press)

  • Bowery NG, Hudson AL, Hill DR, Price GW (1984) Bicuculline-insensitive GABAB receptors. In: Paton W, Mitchell J, Turner P (eds) Proceedings of JUPHAR 9th int congress of pharmacol, London, vol 60. Macmillan, London, pp 159–170

    Google Scholar 

  • Chesselet MF (1984) Presynaptic regulation of neurotransmitter release in the brain: facts and hypothesis. Neurosci 12: 347–375

    Google Scholar 

  • Cuello AC (ed) (1982) Co-transmission. Macmillan, London

    Google Scholar 

  • Enna SJ (ed) (1983) The GABA-receptors, Humana Press, Clifton, NJ

    Google Scholar 

  • Foote SL, Bloom FE, Aston-Jones G (1983) Nucleus locus coeruleus: new evidence of anatomical and physiological specificity. Physiol Rev 63: 844–914

    PubMed  Google Scholar 

  • Fung SC, Fillenz M (1983) The role of pre-synaptic GABA and benzodiazepine receptors in the control of noradrenaline release in rat hippocampus. Neurosci Lett 42: 61–66

    PubMed  Google Scholar 

  • Glowinski J, Iversen LL (1966) Regional studies of catecholamines in the rat brain — I. The disposition of [3H]norepinephrine, [3H]dopamine and [3H]DOPA in various regions of the brain. J Neurochem 13: 655–669

    PubMed  Google Scholar 

  • Hökfelt T, Johansson O, Ljungdahl å, Lundberg JM, Schultzberg M (1980) Peptidergic neurones. Nature 284: 515–521

    PubMed  Google Scholar 

  • Petersen GL (1977) A simplification of the protein assay method of Lowryet al. which is more generally applicable. Anal Biochem 83: 346–356

    PubMed  Google Scholar 

  • Raiteri M, Angelini F, Levi G (1974) A simple apparatus for studying the release of neurotransmitters from synaptosomes. Eur J Pharmacol 25: 411–414

    PubMed  Google Scholar 

  • Raiteri M, Levi G (1978) Release mechanisms for catecholamines and serotonin in synaptosomes. In: Ehrenpreis S, Kopin I (eds) Reviews of neuroscience. Raven Press, New York, pp 77–130

    Google Scholar 

  • Raiteri M, Marchi M, Maura G (1984) Release of catecholamines, serotonin, and acetylcholine from isolated brain tissue. In: Lajtha A (ed) Handbook of neurochemistry, vol 6. Plenum, pp 431–462

  • Rappaport A, Sturtz F, Guicheney P (1985) Regulation of centralα-adrenoceptors by serotoninergic denervation. Brain Res 344: 158–161

    PubMed  Google Scholar 

  • Smith CB, Hollingsworth PJ, GeerJJ, Moises HC (1981) Changes in alpha-2 adrenoceptors in rat brain after long-term tricyclic anti-depressant drug treatment. Brain Res 210: 413–418

    PubMed  Google Scholar 

  • Smith JE, Lane JD, Shea PA, McBride WJ, Aprison MH (1975) A method for concurrent measurement of picomole quantities of acetylcholine, choline, dopamine, norepinephrine, serotonin, 5-hydroxytryptophan, 5-hydroxyindoleacetic acid, tryptophan, tyrosine, glycine, aspartate, glutamate, alanine and gamma-aminobutyric acid in single tissue samples from different areas of rat central nervous system. Anal Biochem 64: 149–169

    PubMed  Google Scholar 

  • Van der Zee P, Koger HS, Gootjes J, Hespe W (1980) Aryl 1,4-dialk(en)ylpiperazines as selective and very potent inhibitors of dopamine uptake. Eur J Med Chem 15: 363–370

    Google Scholar 

  • Yunger LM, Fowler PJ, Zarevics P, Setler PE (1984) Novel inhibitors ofγ-aminobutyric acid (GABA) uptake: anticonvulsant actions in rats and mice. J Pharmacol Exp Ther 228: 109–115

    PubMed  Google Scholar 

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Bonanno, G., Raiteri, M. A carrier for GABA uptake exists on noradrenaline nerve endings in selective rat brain areas but not on serotonin terminals. J. Neural Transmission 69, 59–70 (1987). https://doi.org/10.1007/BF01244097

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  • DOI: https://doi.org/10.1007/BF01244097

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