On the inhibition of GABA release from a preparation of rat brain nerve-endings by SKF 89976-A, a GABA uptake inhibitor.
Fractions enriched in nerve-terminals were made in order to investigate the release of gamma-aminobutyric acid (GABA). A P2-preparation made from whole rat brain was pre-labeled with [3H]GABA and thereafter incubated in high concentrations (1 mM) of the GABA uptake inhibitor SKF 89976-A. The nerve-terminals were thereafter incubated in depolarizing concentrations of KCl and finally the medium and nerve-terminals separated by a filtration procedure. The amount of [3H]GABA present on the filter and in the supernatant was measured by liquid scintillation counting and used to assess the release rate. SKF 89976-A reduced the KCl-induced efflux of [3H]GABA from the nerve-terminals. The inhibition was as effective against KCl-induced [3H]GABA efflux in the presence as well as in the absence of Ca2+. Our finding may demonstrate an inhibition of the inside-out activity of the GABA transporter.
Swedish Defence Research Establishment, Umeå.
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Sellström
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Rassin
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002122:Calcium Chloride / Q000378:metabolism; D005260:Female; D018756:GABA Antagonists; D009411:Nerve Endings / Q000378:metabolism*; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D009557:Nipecotic Acids / Q000494:pharmacology*; D011189:Potassium Chloride / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D018756:GABA Antagonists; D014179:Neurotransmitter Uptake Inhibitors; D009557:Nipecotic Acids; D005680:gamma-Aminobutyric Acid; D011189:Potassium Chloride; C045598:N-(4,4-diphenyl-3-butenyl)nipecotic acid; D002122:Calcium Chloride