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 (2Hz) in a concentration-dependent manner, with similar potencies (phaclofen EC50=0.3mmol/l, 4-ABPA EC50=0.4mmol/l). At 3mmol/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 (3mmol/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 GABAB 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 GABAB heteroreceptors, the lack of effect of 3-APPA and 2-CPEPA on [3H]-GABA release in this study suggests that GABAB autoreceptors may be pharmacologically distinct from the heteroreceptors.
Similar content being viewed by others
Author information
Authors and Affiliations
Additional information
Received: 11 June 1997 / Accepted: 6 January 1998
Rights and permissions
About this article
Cite this article
Ong, J., Marino, V., Parker, D. et al. Differential effects of phosphonic analogues of GABA on GABAB autoreceptors in rat neocortical slices. Naunyn-Schmiedeberg's Arch Pharmacol 357, 408–412 (1998). https://doi.org/10.1007/PL00005186
Issue Date:
DOI: https://doi.org/10.1007/PL00005186