Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Investigations on GABAB receptor-mediated autoinhibition of GABA release

  • 30 Accesses

  • 17 Citations


In this study, we have investigated the effects of phaclofen on the [3H] overflow from [3H]GABA prelabelled rat cortical slices and its interaction with the effects of (−)-baclofen in dependence of the stimulation frequency. (−)-Baclofen strongly depressed the [3H] overflow in the frequency range of 0.125 to 4 Hz to a constant residual level (ICIn50 = 0.37 μmol/l at 0.125 Hz), but became inactive above. The potency of the (+)-enantiomer was considerably weaker by a factor of nearly 1000. The GABAB antagonist, phaclofen, increased [3H] overflow at 300 μmol/l and, moremarkedly, at 3 and 1 mmol/l, respectively. However, the increase was virtually independent of the frequency between 0.125 and 16 Hz. If the compound interacted only with the putative GABAB autoreceptor involved in the regulation of GABA release, the extent of the enhancing effect should increase with increasing frequency because of the concomitant rise in synaptic GABA concentration. In order to further investigate this phenomenon, the IC50 of (−)-baclofen and antagonism of phaclofen against (−)-baclofen were determined at 0.125 Hz and 2 Hz, respectively. Whereas the IC50 of (−)-baclofen was 0.63 ± 0.04 μmol/l at 0.125 Hz, it increased to 4.88 + 0.45 μmol/l at 2 Hz. The pA10-values of phaclofen were about the same at both frequencies, whereas the pA2-values differed by a factor of 2.3. Therefore, the possibility should be considered that (−)-baclofen does not only interact with presynaptic GABA autoreceptors, but also may interact with other - presumably somatodendritic- GABAB-receptors whose pharmacology is not identical with that of the receptors by which (−)-baclofen exerts its effects on GABA release.

This is a preview of subscription content, log in to check access.


  1. Anderson RA, Mitchell R (1985) Evidence for GABAB autoreceptors in median eminence. Eur J Pharmacol 118:3355–3358

  2. Arbilla S, Kamal L, Langer SZ (1979) Presynaptic GABA autoreceptors on GABA-ergic nerve endings of the rat substantia nigra. Eur J Pharmacol 57: 211–217

  3. Baumann PA (1985) Differential selectivity of neuroleptic drugs for presynaptic dopamine autoreceptors and postsynaptic dopamine receptors in rat striatum. Naunyn-Schmiedeberg's Arch Pharmacol (Suppl) 329: R95

  4. Baumann PA, Waldmeier PC (1981) Further evidence for negative feedback control of serotonin release in the central nervous system. Naunyn-Schmiedeberg's Arch Pharmacol 317:36–43

  5. Bonnanno G, Fontana G, Raiteri M (1988) Phaclofen antagonizes GABA at autoreceptors regulating release in rat cerebral cortex. Eur J Pharmacol 154:223–224

  6. Chakravarti IM (1971) Confidence set for the ratio of means of two normal distributions. Biometr Ztschr 13:89–94

  7. Dunnett CW (1955) A multiple procedure for comparing several treatments with a control. J Am Stat Assoc 50: 1096–1121

  8. Dunnett CW (1964) New tables for multiple comparisons with a control. Biometrics 20:482–491

  9. Dutar P, Nicoll RA (1988a) A physiological role for GABAB receptors in the central nervous system. Nature 332:1156–1158

  10. Dutar P, Nicoll RA (1988b) Pre- and postsynaptic GABAB receptors in the hippocampus have different pharmacological properties. Neuron 1:585–591

  11. Farnebo LO (1971) Release of monoamines evoked by field stimulation. Studies on some ionic and metabolic requirements. Acta Physiol Scand Suppl 371:19–27

  12. Giudicelli J-F (1971) Technical note No. 16: Calcul des pAx. J Pharmacol (Paris) 2:373–380

  13. Karlsson G, Pozza M, Olpe H-R (1988) Phaclofen: a GABAB blocker reduces long-duration inhibition in the neocortex. Eur J Pharmacol 148:485–486

  14. Kerr DJ, Ong J, Prager RH, Gynther BD, Curtis DR (1987) Phaclofen: a peripheral and central baclofen antagonist. Brain Res 405:150–154

  15. Kuriyama K, Kanmori K, Taguchi J, Yoneda Y (1984) Stress-induced enhancement of suppression of [3H]GABA release from striatal slices by presynaptic autoreceptors. J Neurochem 42: 943–950

  16. Limberger N, Spath L, Starke K (1986) A search for receptors modulating the release of γ-[3H]aminobuteric acid in rabbit caudate nucleus slices. J Neurochem 46:1109–1117

  17. Mitchell PR, Martin IL (1978) Is GABA release modulated by presynaptic receptors? Nature 274:904–905

  18. Pittaluga A, Asaro D, Pellegrini G, Raiteri M (1987) Studies on [3H]GABA and endogenous GABA release in rat cerebral cortex suggest the presence of autoreceptors on GABAB type. Eur J Pharmacol 144:45–52

  19. Waldmeier PC, Wicki P, Feldtrauer JJ, Baumann PA (1988) Potential involvement of a baclofen-sensitive autoreceptor in the modulation of the release of endogenous GABA from rat brain slices in vitro. Naunyn-Schmiedeberg's Arch Pharmacol 337: 289–295

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

Download references

Author information

Additional information

Send offprint requests to P. A. Baumann at the above address

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Baumann, P.A., Wicki, P., Stierlin, C. et al. Investigations on GABAB receptor-mediated autoinhibition of GABA release. Naunyn-Schmiedeberg's Arch Pharmacol 341, 88–93 (1990). https://doi.org/10.1007/BF00195063

Download citation

Key words

  • GABA release
  • Electrical stimulation
  • Cortex slices
  • GABAB autoreceptor
  • Baclofen
  • Phaclofen