Article date: February 1989
By: Giambattista Bonanno, Paolo Cavazzani, Gian Carlo Andrioli, Daniela Asaro, Graziella Pellegrini, Maurizio Raiteri in Volume 96, Issue 2, pages 341-346
The depolarization‐evoked release of γ‐aminobutyric acid (GABA) and its modulation mediated by autoreceptors were investigated in superfused synaptosomes prepared from fresh human cerebral cortex.
The release of [3H]‐GABA provoked by 15 mM K+ from human cortex nerve endings was almost totally (85%) calcium‐dependent.
In the presence of the GABA uptake inhibitor SK&F 89976A (N‐(4,4‐diphenyl‐3‐butenyl)‐nipecotic; acid), added to prevent carrier‐mediated homoexchange, GABA (1–10 μm) decreased in a concentration‐dependent manner the K+‐evoked release of [3H]‐GABA. The effect of GABA was mimicked by the GABAB receptor agonist (−)‐baclofen (1–100 μm) but not by the GABAA receptor agonist muscimol (1–100 μm). Moreover, the GABA‐induced inhibition of [3H]‐GABA release was not affected by two GABAA receptor antagonists, bicuculline or SR 95531 (2‐(3′‐carbethoxy‐2′‐propenyl)−3‐amino‐6‐paramethoxy‐phenyl‐pyridazinium bromide).
(−)‐Baclofen also inhibited the depolarization‐evoked release of endogenous GABA from human cortical synaptosomes.
It is concluded that GABA autoreceptors regulating the release of both newly taken up and endogenous GABA are present in human brain and appear to belong to the GABAB subtype.
The depolarization‐evoked release of γ‐aminobutyric acid (GABA) and its modulation mediated by autoreceptors were investigated in superfused synaptosomes prepared from fresh human cerebral cortex.
The release of [3H]‐GABA provoked by 15 mM K+ from human cortex nerve endings was almost totally (85%) calcium‐dependent.
In the presence of the GABA uptake inhibitor SK&F 89976A (N‐(4,4‐diphenyl‐3‐butenyl)‐nipecotic; acid), added to prevent carrier‐mediated homoexchange, GABA (1–10 μm) decreased in a concentration‐dependent manner the K+‐evoked release of [3H]‐GABA. The effect of GABA was mimicked by the GABAB receptor agonist (−)‐baclofen (1–100 μm) but not by the GABAA receptor agonist muscimol (1–100 μm). Moreover, the GABA‐induced inhibition of [3H]‐GABA release was not affected by two GABAA receptor antagonists, bicuculline or SR 95531 (2‐(3′‐carbethoxy‐2′‐propenyl)−3‐amino‐6‐paramethoxy‐phenyl‐pyridazinium bromide).
(−)‐Baclofen also inhibited the depolarization‐evoked release of endogenous GABA from human cortical synaptosomes.
It is concluded that GABA autoreceptors regulating the release of both newly taken up and endogenous GABA are present in human brain and appear to belong to the GABAB subtype.
DOI: 10.1111/j.1476-5381.1989.tb11823.x
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