Endogenous dopamine (DA) release was measured in perfused rat retinae. Perfusion with elevated potassium (40 mM K) resulted in a 5-6-fold increase in DA release over baseline or 11.6 +/- 0.9% of final tissue DA content. When the selective DA D2 receptor agonist quinpirole was added to the perfusion medium (at 1 and 10 microM), K-stimulated DA release was significant decreased compared to controls (to 7.0 +/- 1.6 and 6.14 +/- 1.4%, respectively). Addition of the D2 antagonist (+/-)-sulpiride (10 microM) significantly increased DA release to 19.1 +/- 1.3%. DA could be released with successive pulses of K; an initial 10 min pulse resulted in a 4-5-fold increase in endogenous DA release over basal levels or 11.4% of the final retinal tissue DA content and a 3-fold increase (a 9.3% fractional release) upon a second K stimulation given 50 min later. The ratio of stimulated DA release during the two K pulses was 0.82 +/- 0.04. When L-tyrosine (100 microM) was included in the medium throughout the perfusion, K2/K1 was increased to 1.14 +/- 0.13. Both tissue DA level and release were decreased by the tyrosine hydroxylase inhibitor, alpha-methyl-p-tyrosine (AMPT). At 10 microM AMPT K-stimulated DA release was reduced by 50% during the first pulse and completely abolished during the second K pulse. At 100 microM both basal and K-stimulated release were significantly reduced. Exposure of dark-adapted retinae to light in L-tyrosine-supplemented perfusion medium resulted in an increased release of DA compared to retinae perfused with tyrosine-free medium.(ABSTRACT TRUNCATED AT 250 WORDS)