Induced release of gamma-aminobutyric acid by a carrier-mediated, high-affinity uptake of L-glutamate in cultured chick retina cells

: [3H]γ‐aminobutyric acid (GABA) was taken up by cultured embryonic retina cells during the initial stages of cell differentiation. The accumulated GABA was released in the bathing medium and a transient increase in the efflux of GABA was observed when cultures were pulse‐stimulated (2 min) with 0.1 mM L‐glutamate but not with D‐glutamate. The EC50 for L‐glutamate to evoke [3H]GABA release was approximately 15 μM. This value is close to the Km for high‐affinity uptake of L‐glutamate by retina cells. When Na+ ions were replaced by Li+ ions, L‐glutamate‐induced release of GABA was abolished. Moreover. L‐[14C]glutamate uptake by retina cells was significantly reduced when NaCl was replaced by LiCl in the incubation medium. L‐Glutamate elicited release of GABA was Ca2+ independent, and was observed when Ca2+ was replaced by Co2+ or when Mg2+ ions were increased to 10 mM concentration. D‐Aspartate, which is taken up by the same high‐affinity uptake mechanism as L‐glutamate, induced an increase in [3H]GABA efflux comparable to L‐glutamate. The addition of unlabeled GABA to the medium also promoted the release of accumulated [3H]GABA. However, GABA was twofold less effective than L‐glutamate in eliciting [3H]GABA release. The addition of both GABA and L‐glutamate to the incubation medium indicated that [3H]GABA efflux due to L‐glutamate and GABA was additive. L‐Aspartate also promoted an increase in the efflux of [3H]GABA accumulated by retina cells. However, L‐aspartate effect was significantly decreased in the absence of Ca2+ or when Na+ ions were replaced by Li+. Our results indicate that at least three releasable pools of GABA are present in the chick embryo retina cells: (a) a GABA‐promoted GABA release‐homoexchange, (b) a Ca2+‐dependent L‐aspartate‐promoted release, and (c) a Ca2+‐independent, Na+‐dependent L‐glutamate‐evoked release. In addition, our data strongly suggest that the L‐glutamate‐promoted GABA release is due to a process of exchange of L‐glutamate with GABA, which may play a fundamental role in the fine control of the excitability of local circuits in the retina.