Release‐regulating autoreceptors of the GABAB‐type in human cerebral cortex

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Abstract
1 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. 2 The release of [3H]-GABA provoked by 15 mM K+ from human cortex nerve endings was almost totally (85%) calcium-dependent. 3 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). 4 (−)-Baclofen also inhibited the depolarization-evoked release of endogenous GABA from human cortical synaptosomes. 5 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.