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Differential effects of phosphonic analogues of GABA on GABA(B) autoreceptors in rat neocortical slices.
- Source :
-
Naunyn-Schmiedeberg's archives of pharmacology [Naunyn Schmiedebergs Arch Pharmacol] 1998 Apr; Vol. 357 (4), pp. 408-12. - Publication Year :
- 1998
-
Abstract
- The effects of five phosphonic derivatives of GABA on the release of [3H]-GABA from rat neocortical slices, preloaded with [3H]-GABA, were investigated. Phaclofen and 4-aminobutylphosphonic acid (4-ABPA) increased the overflow of [3H] evoked by electrical stimulation (2 Hz) in a concentration-dependent manner, with similar potencies (phaclofen EC50=0.3 mmol/l, 4-ABPA EC50=0.4 mmol/l). At 3 mmol/l, phaclofen increased the release of [3H]-GABA by 82.6+/-8.6%, and 4-ABPA increased the release by 81.3+/-9.0%. 2-Amino-ethylphosphonic acid (2-AEPA) increased the overflow of [3H] by 46.8+/-10.9% at the highest concentration tested (3 mmol/l). In contrast, the lower phosphonic homologue 3-aminopropylphosphonic acid (3-APPA), and 2-amino-2-(p-chlorophenyl)-ethylphosphonic acid (2-CPEPA), a baclofen analogue, did not modify the stimulated overflow. These results suggest that phaclofen, 4-ABPA and 2-AEPA are antagonists at GABA(B) autoreceptors, the latter being the weakest antagonist, whilst neither 3-APPA nor 2-CPEPA are active at these receptors. Since phaclofen, 4-ABPA and 2-CPEPA are antagonists and 3-APPA a partial agonist/antagonist on GABA(B) heteroreceptors, the lack of effect of 3-APPA and 2-CPEPA on [3H]-GABA release in this study suggests that GABA(B) autoreceptors may be pharmacologically distinct from the heteroreceptors.
- Subjects :
- Animals
Butylamines pharmacology
Kainic Acid analogs & derivatives
Kainic Acid pharmacology
Male
Neocortex metabolism
Organophosphorus Compounds pharmacology
Propylamines pharmacology
Rats
Rats, Sprague-Dawley
Receptors, GABA-B metabolism
gamma-Aminobutyric Acid pharmacology
GABA Antagonists pharmacology
Neocortex drug effects
Receptors, GABA-B drug effects
gamma-Aminobutyric Acid analogs & derivatives
Subjects
Details
- Language :
- English
- ISSN :
- 0028-1298
- Volume :
- 357
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Naunyn-Schmiedeberg's archives of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 9606026
- Full Text :
- https://doi.org/10.1007/pl00005186