L-glutamate evoked release of GABA from cultured avian retina cells does not require glutamate receptor activation.

gamma-Aminobutyric acid (GABA) and L-glutamate are the major inhibitory and excitatory transmitters in the central nervous system. Recent evidence has indicated that L-glutamate may stimulate GABA release by a novel exchange mechanism (Nascimento and De Mello, J. Neurochem., 1985, 45: 1820-1827). Here we provide strong support for this hypothesis by showing that the L-glutamate-evoked release of [3H]GABA from cultured avian retina cells is not dependent on the activation of excitatory amino acid receptors. Retina cells were found to incorporate [3H]GABA into a pool that was released when cultures were treated with L-glutamate (100 microM). This release was unaffected when calcium ions were removed, but was prevented when NaCl was replaced by LiCl. D-Aspartate, which in tracer experiments was shown to be taken into cells by the same carrier as L-glutamate, was also able to evoke release of [3H]GABA, with the same requirement for NaCl. In addition, L-glutamate and D-aspartate uptake by retina cells was inhibited in more then 80% when the uptake was measured in the presence of LiCl. As opposed to GABA, the release of acetylcholine (ACh) promoted by L-glutamate showed characteristics of classical mechanisms of neurotransmitter release. Glutamate-induced efflux of ACh was Ca2+-dependent and was not affected when NaCl was replaced by LiCl. Also, D-aspartate was ineffective in eliciting the release of ACh. Even at high concentrations, antagonists of excitatory amino acid receptors were unable to diminish the glutamate-evoked release of [3H]GABA.(ABSTRACT TRUNCATED AT 250 WORDS)