Somatostatin (SRIF) influences the release of two important neuromodulators of retinal circuitry, dopamine (DA) and nitric oxide (NO). The aim of the present study was to examine whether DA and NO modulate SRIF release in rat retina, and the mechanisms involved in their actions. Retinas of adult female Sprague--Dawley rats (250--300 g) were mechanically detached from the eyecup and ex vivo experiments were performed. Retinal explants were incubated in the presence of dopaminergic [DA (10 microM, 100 microM and 200 microM), apomorphine (nonselective D1/D2 agonist, 0.50 mM, 1.0 microM and 10 microM), A68930 (D1 selective agonist, 0.50 microM, 1.0 microM and 10 microM), quinpirole (D2 selective agonist, 0.50 microM, 1.0 microM and 10 microM), SCH 23390 (D1 selective antagonist, 250 nM and 500 nM) and sulpiride (D2 selective antagonist, 100 microM and 200 microM)], and nitrinergic agents [arginine (62.5 microM--5mM), SIN-1 (50 microM, 100 microM and 500 microM) and 8-Br-cGMP (50 microM, 250 microM and 500 microM)]. SRIF levels were quantified using radioimmunoassay (RIA). Dopamine had no effect on SRIF levels. Apomorphine produced a concentration dependent decrease and increase in SRIF levels, suggestive of pre- and postsynaptic effects. A68930 (10 microM) and SCH 23390 (250 nM and 500 nM) mimicked and reversed apomorphine's postsynaptic actions, respectively. Quinpirole had no effect, but blockade of D2 autoreceptors by sulpiride (200 microM) afforded an increase in SRIF levels. Arginine and SIN-1 increased, and 8-Br-cGMP attenuated SRIF levels. These results show that dopamine D1 receptors, and NO/peroxynitrite agents modulate SRIF release in the retina suggesting that the triad SRIF--DA--NO have reciprocal interactions via which they regulate retinal circuitry and vision transduction.