ABSTRACT
1. In the rat retina, gamma-aminobutyric acid (GABA) released as a transmitter is inactivated by uptake mainly into glial cells (Müller cells). Activation of P2-purinoceptors in Müller cells increases [Ca2+]i and the present study was undertaken to see whether this action affected the glial release of [3H]-GABA from the superfused rat isolated retina. 2. Adenosine 5'-triphosphate (ATP) and the P2X-purinoceptor agonists, alpha,beta-methylene-ATP (alpha,beta-meATP) and beta,gamma-methyleneATP (beta,gamma-meATP) significantly increased the KCl-evoked release of [3H]-GABA from the retina. 3. Adenosine and the P2Y-purinoceptor agonist, 2-chloroATP, had no effect on the KCl-evoked release of [3H]-GABA from the retina. However, 2-methylthioATP (2-Me-S-ATP) significantly enhanced the evoked release of [3H]-GABA. 4. The effect of ATP on the glial release of [3H]-GABA was abolished by the P2-antagonist, pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS). 5. When the superfused retina was exposed to the GABA uptake inhibitor, SKF89976A, the enhancing effect of alpha,beta-meATP on the KCl-evoked release of GABA was abolished. 6. The KCl-evoked release of [3H]-GABA from the frog retina and rat cerebrocortical slices, which take up GABA mainly into neurones, was not affected by ATP or alpha,beta-meATP. 7. We concluded that the glial Müller cells in the rat retina possess P2-receptors, activation of which increases the 'release' of preloaded [3H]-GABA apparently by reducing uptake. On balance, the results suggest the involvement of P2X-purinoceptors, although we cannot exclude the possibility that P2Y-purinoceptors may be involved. Our results suggest that ATP, as well as being a conventional transmitter in the retina, may be involved in neuronal-glial signalling and modulate the extracellular concentration of GABA.
