ISSN:
1432-1912
Keywords:
Key words Rat neocortical slices
;
GABABautoreceptors
;
[3H]-GABA release
;
GABAB receptor antagonists
;
Phosphonic analogues of GABA
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/PL00005186
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