Multiple neurotransmitter systems influence the release of adenosine derivatives from the rabbit retina

Rabbit retinac preloaded with [(3)H]adenosine were superfused in vitro and the effect of neurotransmitter agonists and antagonists on the release of [(3)H]purines was studied. Glutamic acid, aspartic acid, kainic acid (KA), quisqualic acid (QUIS) and N- methyl- d -aspartic acid (NMDA) all stimulated the efflux of [(3)H] labelled and endogenous purines. Their effect was reduced in a Ca(2+)-free medium except when using a high concentration (100 ?M) of KA, QUIS and NMDA. The effect of aspartic acid and of NMDA were blocked by 2-amino-7-phosphono-heptanoic acid (APH) and 2-amino-5-phosphono-valeric acid (APV). Carbachol also increased the release of adenosine-derived radioactivity and this effect was reduced by the removal of Ca(2+) and by pretreatment with atropine. ?-Aminobutyric acid (GABA) and muscimol, induced a small increase in the release which was Ca(2+)-dependent and was blocked by bicuculline and picrotoxin. Dopamine elicited an increase in the release which was partially reduced in a Ca(2+)-free medium and was blocked by haloperidol. Glycine and 5-hydroxytryptamine (5-HT) also induced small but significant increases. The neurotransmitter antagonists had an effect of their own. Superfusion with APH and APV depressed the outflow of radioactivity whereas bicuculline, picrotoxin, strychnine and haloperidol enhanced it. The K(+)-evoked release of [(3)H]purines was reduced by haloperidol and by 5-HT. The observations indicate that stimulation of several important neurotransmitter receptors in the retina elicits the release of adenosine derivatives. The results with the antagonists also suggest that purines are continuously released as a result of a tonic activation of the respective membrane receptors.