—A rapid accumulation of [3H]GABA occurs in slices of rat cerebral cortex incubated at 25° or 37° in a medium containing [3H]GABA. Tissue medium ratios of almost 100:1 are attained after a 60 min incubation at 25°. At the same temperature no labelled metabolites of GABA were found in the tissue or the medium. The process responsible for [3H]GABA uptake has many of the properties of an active transport mechanism: it is temperature sensitive, requires the presence of sodium ions in the external medium, is inhibited by dinitrophenol and ouabain, and shows saturation kinetics. The estimated Km value for GABA is 2·2 × 10−5m, and Vmax is 0·115 μmoles/min/g cortex. There is only negligible efflux of the accumulated [3H]GABA when cortical slices are exposed to a GABA‐free medium. [3H]GABA uptake was not affected by the presence of large molar excesses of glycine, l‐glutamic acid, l‐aspartic acid, or β‐aminobutyrate, but was inhibited in the presence of l‐alanine, l‐histidine, β‐hydroxy‐GABA and β‐guanidinopropionate. It is suggested that the GABA uptake system may represent a possible mechanism for the inactivation of GABA or some related substance at inhibitory synapses in the cortex.

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The retina is an area of the central nervous system that possesses intrinsic cholinergic neurones which release acetylcholine (ACh) in response to stimulation with flickering light. Using an eye-cup preparation in anaesthetized rabbits we found that when the retina was exposed to the P2-purinoceptor antagonist, PPADS, the light-evoked release of ACh was strikingly increased (by over 40%). In contrast, ATP reduced the -light-evoked release of ACh by 20%. The inhibitory effect of ATP was not due to its catabolism to adenosine because it was not affected by the A,-adenosine receptor antagonist, DPCPX, in combination with adenosine deaminase. The actions of both ATP and PPADS were completely blocked by strychnine. We conclude that during physiological stimulation of the retina with light, ATP is co-released with ACh and partially inhibits ACh release by activating (with ACh) an inhibitory glycinergic feedback loop.

1 The effects ot acute and chronic vigabatrin (y-vinyl-GABA) (GVG) administration on y-aminobutyric acid (GABA) levels and release in rat cortical slices, spinal cord slices and retinas were studied. 2 GVG (250mgkg-1 i.p.) administered to rats 18h before death (acute administration) produced an almost 3 fold increase in GABA levels of the cortex and spinal cord and a 6 fold increase in retinal GABA. The levels of glutamate, aspartate, glycine and taurine were unaffected. 3 When GVG (250mgkg-' i.p.) was administered daily for 17 days (chronic administration) a similar (almost 3 fold) increase in cortical GABA occurred but the increases in spinal and retinal GABA were reduced by approximately 40%. 4 Acute administration of GVG strikingly increased the potassium-evoked release (KCI 50mM) of GABA from all three tissues. This enhanced evoked release was reduced by about 50% in tissues taken from rats that had been chronically treated with GVG. 5 Acute administration of GVG reduced GABA-transaminase (GABA-T) activity by approximately 80% in cortex and cord and by 98% in the retina. Following the chronic administration of GVG, there was a trend for GABA-T activities to recover (significant only in cortex). Acute administration of GVG had no effect on glutamic acid decarboxylase (GAD) activity in cortex or spinal cord. However, chronic treatment resulted in significant decreases in GAD activity in both the cortex and cord (35% and 50% reduction respectively). 6 The K-evoked release of glutamate, aspartate, glycine and taurine from cortical slices and the Kevoked release of glycine from spinal slices and retinas were not affected by either acute or chronic GVG treatment.7 These experiments indicate that GVG treatment increases specifically the K-evoked release of GABA and that tolerance can develop to this enhancing effect of GVG on central GABA release. This tolerance may result from increased feedback inhibition of GAD with a consequent reduction of presynaptic GABA stores.