Lack of coupling between GABA release and GABA synthesis in the rat brain via GABA(B) 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 GABA(B) autoreceptors. The aim of this work was to ascertain whether or not GABA synthesis and release are coupled in the rat brain through a GABA(B) autoreceptor-mediated modulation. It was found that (-)baclofen (30microM) reduces the K+ stimulated release of [3H]GABA in synaptosomes and prisms (10microM) 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 microM (-)baclofen. Similar results on GABA synthesis were also observed when 1-100 microM 3-aminopropil(methyl)phosphinic acid or GABA was used instead of (-)baclofen to stimulate GABA(B) autoreceptors. [3H]GABA release, [3H]GABA synthesis from [3H]glutamine and GAD activity were also insensitive to the action of the GABA(B) antagonist CGP 52432 (10-100microM). Likewise, muscimol (0.3-100microM) did not affect GABA synthesis. Our results indicate that unlike GABA release, GABA synthesis is not modulated by GABA(B) autoreceptors.
Aguilar-García
A
A
Department of Biophysics, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México.
González-Frankenberger
B
B
Ramón-Frías
T
T
Méndez-Franco
B J
BJ
Pérez-de la Mora
M
M
D000818:Animals; D001921:Brain / Q000378:metabolism*; D058786:GABA-B Receptor Agonists; D005973:Glutamine / Q000378:metabolism; D008024:Ligands; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000378:metabolism*; D014316:Tritium; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis* / Q000378:metabolism*
D058786:GABA-B Receptor Agonists; D008024:Ligands; D018080:Receptors, GABA-B; D005973:Glutamine; D014316:Tritium; D005680:gamma-Aminobutyric Acid