Lack of coupling between GABA release and GABA synthesis in the rat brain via GABAB autoreceptors

GABA is synthesized within GABA terminals through a highly compartmentalized process in which glial-derived glutamine is a major precursor and its release is modulated by GABAB autoreceptors. The aim of this work was to ascertain whether or not GABA synthesis and release are coupled in the rat brain through a GABAB autoreceptor-mediated modulation. It was found that (−)baclofen (30 μM) reduces the K+ stimulated release of [3H]GABA in synaptosomes and prisms (10 μM) from cerebral cortex, while at the same concentrations (−)baclofen failed to modify the synthesis of [3H]GABA from [3H]glutamine in cortical and hypothalamic slices, prisms and in cortical synaptosomes. In this latter preparation, identical results were observed when (−)baclofen was added to Krebs-Tris media, containing 5 or 15 mM K+ concentration. In agreement with these latter results, glutamic acid decarboxylase (GAD) activity from cortical and hypothalamic prisms was not affected by 1–100 μM (−)baclofen. Similar results on GABA synthesis were also observed when 1–100 μM 3-aminopropil(methyl)-phosphinic acid or GABA was used instead of (−)baclofen to stimulate GABAB autoreceptors. [3H]GABA release, [3H]GABA synthesis from [3H]glutamine and GAD activity were also insensitive to the action of the GABAB antagonist CGP 52432 (10–100 μM). Likewise, muscimol (0.3–100 μM) did not affect GABA synthesis. Our results indicate that unlike GABA release, GABA synthesis is not modulated by GABAB autoreceptors.