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Human brain somatostatin release from isolated cortical nerve endings and its modulation through GABA B receptors
Author(s) -
Bonanno Giambattista,
Gemignani Anita,
Schmid Giovanna,
Severi Paolo,
Cavazzani Paolo,
Raiteri Maurizio
Publication year - 1996
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 - 10.1111/j.1476-5381.1996.tb15558.x
Subject(s) - muscimol , agonist , baclofen , gabab receptor , somatostatin , chemistry , medicine , receptor , aminobutyric acid , endocrinology , gabaa receptor , gaba receptor , depolarization , biology , biochemistry
1 The release of somatostatin‐like immunoreactivity (SRIF‐LI) in the human brain was studied in synaptosomal preparations from fresh neocortical specimens obtained from patients undergoing neurosurgery to remove deeply sited tumours. 2 The basal outflow of SRIF‐LI from superfused synaptosomes was increased about 3 fold during exposure to a depolarizing medium containing 15 mM KCl. The K + ‐evoked overflow of SRIF‐LI was almost totally dependent on the presence of Ca 2+ in the superfusion medium. 3 The GABA B receptor agonist, (—)‐baclofen (0.3–100 μ m ), inhibited the overflow of SRIF‐LI in a concentration‐dependent manner (EC 50 = 1.84 ± 0.20 μ m ; maximal effect: about 50%). The novel GABA B receptor ligand, 3‐aminopropyl(difluoromethyl)phosphinic acid (CGP 47656) mimicked (—)‐baclofen in inhibiting the SRIF‐LI overflow (EC 50 = 3.06 ± 0.52 μ m ; maximal effect: about 50%), whereas the GABA A receptor agonist, muscimol, was ineffective up to 100 μ m . 4 The inhibition by 10 μ m (—)‐baclofen of the K + ‐evoked SRIF‐LI overflow was concentration‐dependently prevented by two selective GABA B receptor antagonists, 3‐amino‐propyl (diethoxymethyl)‐phosphinic acid (CGP 35348) (IC 50 = 24.40 ± 2.52 μ m ) and [3‐[[(3,4‐dichlorophenyl) methyl]amino]propyl] (diethoxymethyl) phosphinic acid (CGP 52432) (IC 50 = 0.06 ± 0.005 μ m ). 5 The inhibition of SRIF‐LI overflow caused by 10 μ m CGP 47656 was abolished by 1 μ m CGP 52432. 6 When human synaptosomes were labelled with [ 3 H]‐GABA and depolarized in superfusion with 15 mM KCl, the inhibition by 10 μ m (—)‐baclofen of the depolarization‐evoked [ 3 H]‐GABA overflow was largely prevented by 10 μ m CGP 47656 which therefore behaved as an autoreceptor antagonist. 7 In conclusion: (a) the characteristics of SRIF‐LI release from synaptosomal preparations of human neocortex are compatible with a neuronal origin; (b) the nerve terminals releasing the neuropeptide possess inhibitory receptors of the GABA B type; (c) these receptors differ pharmacologically from the GABA B autoreceptors present on human neocortex nerve terminals since the latter have been shown to be CGP 35348‐insensitive but can be blocked by CGP 47656.