INFLUENCE OF CELLULAR TRANSPORT ON THE INTERACTION OF AMINO ACIDS WITH γ‐AMINOBUTYRIC ACID (GABA)‐RECEPTORS IN THE ISOLATED OLFACTORY CORTEX OF THE GUINEA‐PIG

Abstract

1 Freshly cut guinea-pig olfactory cortex slices contained 2.2 mmol γ-aminobutyric acid (GABA)/kg tissue weight. This declined during in vitro incubation at 25°C in the absence of exogenous GABA, but increased to 6.95 mmol/kg after 1.5 h incubation in 1 mm GABA. 2 Uptake of [³H]-GABA (1 μm) was inhibited by 1 mm (±)-nipecotic acid (−83%), β-amino-n-butyric acid (BABA) (−59%), l-2,4-diaminobutyric acid (DABA) (−63%), (±)cis-3-aminocyclohexane carboxylic acid (ACHC) (−53%), and 3-aminopropanesulphonic acid (3-APS) (−26%), but was increased by β-alanine (BALA) (+23%). 3 Autoradiographs showed steep concentration gradients of radioactivity across slices incubated for short periods in [³H]-GABA. 4 Efflux of [³H]-GABA from pre-loaded slices was accelerated strongly by nipecotic acid, BABA, DABA and ACHC but weakly or not all by BALA or 3-APS. 5 Nipecotic acid (1 mm) potentiated the surface-depolarization of the slice produced by GABA but not that produced by 3-APS. 6 The depolarizing actions of DABA, BABA, nipecotic acid and ACHC, but not that of 3-APS or BALA, were potentiated when the endogenous GABA content of slices was raised. 7 It is concluded that: (a) the depolarizing action of exogenous GABA is limited by cellular uptake; (b) surface-depolarizations produced by nipecotic acid, DABA, BABA and ACHC may be mediated by the release of GABA; and (c) neuronal, rather than glial, transport systems are responsible for these effects.