Please use this identifier to cite or link to this item: http://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-Schmiedeberg's 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
RMID: 0030006064
DOI: 10.1007/PL00005186
Appears in Collections:Anaesthesia and Intensive Care publications

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