³H-baclofen and ³H-GABA bind to bicuculline-insensitive GABA_B sites in rat brain

Abstract

The presence of a novel receptor for the neurotransmitter γ-aminobutyric acid (GABA) on peripheral autononric nerve terminals and in mammalian brain slices has been described recently^1–4. This receptor differs from the classical GABA site as it is unaffected by recognized GABA antagonists such as bicuculline and is not sensitive to the majority of accepted GABA-mimetics such as 3-aminopropanesulphonic acid (3-APS) or isoguvacine. We propose to designate the classical site as the GABA_A and the novel site as the GABA_B receptor. The β-p-chlorophenyl derivative of GABA, baclofen, is stereo-specifically active at the GABA_B site whereas it is devoid of activity at the classical GABA_A site^2,5–9. We now report that high-affinity saturable binding of ³H-baclof en and ³H-G AB A to the GABA_B site can be detected in fragments of crude synaptic membranes prepared from rat brain. The results support the concept of a novel GABA receptor within the mammalian brain and show that GABA and baclofen can compete for the same recognition site.