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https://hdl.handle.net/2440/6029
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Type: | Journal article |
Title: | Differential effects of phosphonic analogues of GABA on GABAB autoreceptors in rat neocortical slices |
Author: | Ong, J. Marino, V. Parker, D. Kerr, D. |
Citation: | Naunyn-Schmiedebergs Archives of Pharmacology, 1998; 357(4):408-412 |
Publisher: | Springer-Verlag |
Issue Date: | 1998 |
ISSN: | 1432-1912 1432-1912 |
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. |
Keywords: | Rat neocortical slices GABABautoreceptors [3H]-GABA release GABAB receptor antagonists Phosphonic analogues of GABA |
DOI: | 10.1007/PL00005186 |
Published version: | http://dx.doi.org/10.1007/pl00005186 |
Appears in Collections: | Anaesthesia and Intensive Care publications Aurora harvest |
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