GABA-mediated potentiation of amine release from nigrostriatal dopamine neurones in vitro.
The uptake and release of 3H-dopamine was studied in slices of corpus striatum and substantia nigra in the presence of nialamide. High potassium triggered the outflow of tritium in both brain structures and this release was potentiated by GABA in a dose related fashion, whereas the spontaneous overflow of radioactivity was unchanged. This action of GABA was mimicked by the GABA-T antagonists aminooxyacetic acid and ethanolamine-O-sulphate, but not by the GABA analogues muscimol, 3-aminopropanesulphonic acid, gamma-hydroxybutyrate or beta-(p-chlorophenyl)-GABA. The response to GABA was not blocked by picotoxin, which itself facilitated the evoked release of 3H-dopamine, nor by bicuculline or the omission of calcium ions from the bathing medium. GABA facilitation of K+-evoked 3H-dopamine release was increased significantly on reducing tissue thickness and following prolonged incubation with GABA. GABA also potentiated the depolarization induced outflow of 3H-noradrenaline, 3H-5-hydroxytryptamine and 3H-histamine without affecting their initial accumulation. Veratridine, amphetamine and cold dopamine also raised the output of 3H-dopamine, but none of these releases was altered by GABA. The uptake of 3H-dopamine, but not that of 14C-GABA, was considerably attenuated in 6-hydroxydopamine lesioned corpora striata. The possible mechanism(s) of this stimulatory action of GABA is discussed.
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D006632:Histamine / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000494:pharmacology*
D012701:Serotonin; D005680:gamma-Aminobutyric Acid; D006632:Histamine; D000612:4-Aminobutyrate Transaminase; D004298:Dopamine; D009638:Norepinephrine