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There is evidence that isoprostanes (IsoPs) can regulate sympathetic neurotransmission in bovine irides in vitro (Opere et al., Free Rad Res. 35:2001). However, the regulation of dopamine (DA) levels by IsoPs in mammalian retinae remains unclear. We examined the effect of IsoPs on endogenous DA levels in rabbit, in vivo and on K+-evoked release of exogenously applied [³H]DA release in bovine retinae, in vitro. Albino rabbits were sedated, then injected intravitreally with IsoPs. After 4 hours, animals were sacrificed and retinae isolated for measurement of DA using HPLC. Isolated bovine retinae were incubated in Krebs solution containing 150 nM of [³H]DA for 45 mins and then prepared for studies of neurotransmitter release using the Superfusion Method. In rabbit retina, 8-isoPGF2α (0.1 µM & 10µM) attenuated DA levels by 50% (p<0.05) and 52% (p<0.05) while 8-isoPGE2 (0.1 µM & 10µM) increased DA levels by 56 % (p<0.01) and 107 % (p<0.001). In isolated bovine retinae, 8-isoPGF2α (0.1 µM and 10 µM) attenuated DA release by 25% and 16% while 8-isoPGE2 inhibited the catecholamine by 25% (p<0.05) and 50% (p<0.01) respectively. The effect of both IsoPs on K+-evoked [³H]DA release was reversed by the COX enzyme inhibitor, flubiprofen (3 µM). IsoPs can regulate endogenous DA levels and the release of exogenously applied DA in mammalian retinae. PGs are involved in the inhibitory effect of IsoPs on DA release. [ABSTRACT FROM AUTHOR]