GABAB autoreceptors in rat cortex synaptosomes: response under different depolarizing and ionic conditions.
Rat cerebral cortex synaptosomes prelabeled with [3H]gamma-aminobutyric acid [( 3H]GABA) were exposed in superfusion to various concentrations of KCl (9-50 mM). The evoked release of [3H]GABA reached a plateau at about 35 mM KCl. The K+-induced release was Ca2+-dependent, particularly at the lowest K+ concentrations. The GABAB agonist (-)-baclofen concentration dependently inhibited the release of [3H]GABA evoked by K+; this effect decreased with increasing K+ concentration and disappeared at 35 mM KCl. The GABAA agonist muscimol (1-100 microM) was totally ineffective to inhibit the release of [3H]GABA. Veratrine (1-30 microM) induced the release of [3H]GABA and the effect was tetrodotoxin-sensitive. (-)-Baclofen, but not muscimol, decreased the veratrine-induced [3H]GABA release; the GABAB agonist was particularly effective in presence of low concentrations of veratrine (1-3 microM) but the effect disappeared when 30 microM of the alkaloid was used. The inhibitory effect of (-)-baclofen on the release of [3H]GABA evoked by 15 mM KCl was dependent on the concentration of Ca2+: the effect increased as the concentration of Ca2+ was raised, reaching a plateau at 0.6 mM Ca2+. Exogenous GABA, in presence of the GABA uptake blocker SK & F 89976A, inhibited the release of [3H]GABA evoked by K+; this effect was antagonized by phaclofen. The data support the idea that terminal GABA autoreceptors in the rat cerebral cortex are of the GABAB type.
Bonanno
G
G
Istituto di Farmacologia e Farmacognosia, Università degli Studi di Genova, Italy.
Pellegrini
G
G
Asaro
D
D
Fontana
G
G
Raiteri
M
M
D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism* / Q000648:ultrastructure; D066298:In Vitro Techniques; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism*; D014702:Veratrine / Q000494:pharmacology
D009467:Neuromuscular Depolarizing Agents; D011963:Receptors, GABA-A; C052329:phaclofen; D009118:Muscimol; D011189:Potassium Chloride; D014702:Veratrine; D001418:Baclofen; D002118:Calcium