Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1987 Jul;91(3):517–522. doi: 10.1111/j.1476-5381.1987.tb11244.x

GABAB-receptor mediated inhibition of potassium-evoked release of endogenous 5-hydroxytryptamine from mouse frontal cortex.

J A Gray, A R Green
PMCID: PMC1853550  PMID: 3038240

Abstract

The effect of baclofen, the GABAB-agent, on the potassium-evoked release of endogenous 5-hydroxytryptamine (5-HT) from slices of mouse frontal cortex has been investigated. The release of endogenous 5-HT evoked by addition of K+ (35 mM) was inhibited by (+/-)-baclofen in a dose-dependent manner with an IC50 of 0.1 microM. Inhibition of K+-evoked release of 5-HT was produced by (+/-)- and (-)-baclofen but not (+)-baclofen. This action of the (-)-enantiomer was not altered by the presence of the (+)-enantiomer. Addition of GABA (0.1-10 microM) also induced a dose-dependent inhibition of 5-HT release. This effect was neither enhanced by flurazepam (1 microM) nor antagonized by bicuculline (10 microM). The progabide metabolite, 4-[( (4-chlorophenyl) (5-fluoro-2-hydroxyphenyl)methylene]amino)butyric acid (SL75.102) (1 microM) inhibited the K+-evoked release of 5-HT by 61%. These data suggest that baclofen is a potent inhibitor of the K+-evoked release of endogenous 5-HT from the cortex and further indicate that the release of 5-HT may be controlled by a GABAB-receptor located presynaptically.

Full text

PDF

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Auerbach S., Lipton P. Regulation of serotonin release from the in vitro rat hippocampus: effects of alterations in levels of depolarization and in rates of serotonin metabolism. J Neurochem. 1985 Apr;44(4):1116–1130. doi: 10.1111/j.1471-4159.1985.tb08733.x. [DOI] [PubMed] [Google Scholar]
  2. Gray J. A., Metz A., Goodwin G. M., Green A. R. The effects of the GABA-mimetic drugs, progabide and baclofen, on the biochemistry and function of 5-hydroxytryptamine and noradrenaline. Neuropharmacology. 1986 Jul;25(7):711–716. doi: 10.1016/0028-3908(86)90086-9. [DOI] [PubMed] [Google Scholar]
  3. Green A. R. Changes in gamma-aminobutyric acid biochemistry and seizure threshold. Ann N Y Acad Sci. 1986;462:105–119. doi: 10.1111/j.1749-6632.1986.tb51245.x. [DOI] [PubMed] [Google Scholar]
  4. Herdon H., Strupish J., Nahorski S. R. Differences between the release of radiolabelled and endogenous dopamine from superfused rat brain slices: effects of depolarizing stimuli, amphetamine and synthesis inhibition. Brain Res. 1985 Dec 2;348(2):309–320. doi: 10.1016/0006-8993(85)90450-0. [DOI] [PubMed] [Google Scholar]
  5. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  6. Lloyd K. G., Arbilla S., Beaumont K., Briley M., De Montis G., Scatton B., Langer S. Z., Bartholini G. gamma-Aminobutyric acid (GABA) receptor stimulation. II. Specificity of progabide (SL 76002) and SL 75102 for the GABA receptor. J Pharmacol Exp Ther. 1982 Mar;220(3):672–677. [PubMed] [Google Scholar]
  7. Molyneux S. G., Clarke E. E. Precise determination of 5-hydroxytryptamine in platelets and platelet-poor plasma. Clin Chem. 1985 Sep;31(9):1573–1574. [PubMed] [Google Scholar]
  8. Newberry N. R., Nicoll R. A. Comparison of the action of baclofen with gamma-aminobutyric acid on rat hippocampal pyramidal cells in vitro. J Physiol. 1985 Mar;360:161–185. doi: 10.1113/jphysiol.1985.sp015610. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Scatton B., Serrano A., Rivot J. P., Nishikawa T. Inhibitory GABAergic influence on striatal serotonergic transmission exerted in the dorsal raphe as revealed by in vivo voltammetry. Brain Res. 1984 Jul 9;305(2):343–352. doi: 10.1016/0006-8993(84)90440-2. [DOI] [PubMed] [Google Scholar]
  10. Schlicker E., Classen K., Göthert M. GABAB receptor-mediated inhibition of serotonin release in the rat brain. Naunyn Schmiedebergs Arch Pharmacol. 1984 Jun;326(2):99–105. doi: 10.1007/BF00517304. [DOI] [PubMed] [Google Scholar]
  11. Worms P., Depoortere H., Durand A., Morselli P. L., Lloyd K. G., Bartholini G. gamma-Aminobutyric acid (GABA) receptor stimulation. I. Neuropharmacological profiles of progabide (SL 76002) and SL 75102, with emphasis on their anticonvulsant spectra. J Pharmacol Exp Ther. 1982 Mar;220(3):660–671. [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES