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Pharmacologically distinct GABA B receptors that mediate inhibition of GABA and glutamate release in human neocortex
Author(s) -
Bonanna Giambattisa,
Fassio Anna,
Schmid Giovanna,
Severi Paolo,
Sala Robery,
Raiteri Maurizio
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0700852
Subject(s) - glutamate receptor , baclofen , agonist , autoreceptor , gabab receptor , aminobutyric acid , chemistry , gaba receptor , gabaa receptor , pharmacology , glutamic acid , nmda receptor , glutamatergic , medicine , biology , receptor , biochemistry , amino acid
The release of endogenous γ‐aminobutyric acid (GABA) and glutamic acid in the human brain has been investigated in synaptosomal preparations from fresh neocortical samples obtained from patients undergoing neurosurgery to reach deeply located tumours. The basal outflows of GABA and glutamate from superfused synaptosomes were largely increased during depolarization with 15 m m KCl. The K + ‐evoked overflows of both amino acids were almost totally dependent on the presence of Ca 2+ in the superfusion medium. The GABA B receptor agonist (−)‐baclofen (1, 3 or 10 μ m ) inhibited the overflows of GABA and glutamate in a concentration‐dependent manner. The inhibition caused by 10 μ m of the agonist ranged from 45–50%. The effect of three selective GABA B receptor antagonists on the inhibition of the K + ‐evoked GABA and glutamate overflows elicited by 10 μ m (−)‐baclofen was investigated. Phaclofen antagonized (by about 50% at 100 μ m ; almost totally at 300 μ m ) the effect of (−)‐baclofen on GABA overflow but did not modify the inhibition of glutamate release. The effect of (−)‐baclofen on the K + ‐evoked GABA overflow was unaffected by 3‐amino‐propyl (diethoxymethyl)phosphinic acid (CGP 35348; 10 or 100 μ m ); however, CGP 35348 (10 or 100 μ m ) antagonized (−)‐baclofen (complete blockade at 100 μ m ) at the heteroreceptors on glutamatergic terminals. Finally, [3‐[[(3,4‐dichlorophenyl) methyl]amino]propyl] (diethoxymethyl) phosphinic aid (CGP 52432), 1 μ m , blocked the GABA B autoreceptor, but was ineffective at the heteroreceptors. The selectivity of CGP 52432 was lost at 30 μ m , as the compound, at this concentration, inhibited completely the (−)‐baclofen effect both on GABA and glutamate release. It is concluded that GABA and glutamate release evoked by depolarization of human neocortex nerve terminals can be affected differentially through pharmacologically distinct GABA B receptors.British Journal of Pharmacology (1997) 120 , 60–64; doi: 10.1038/sj.bjp.0700852