Atypical effect of dopamine in modulating the functional inhibition of NMDA receptors of cultured retina cells

Cultured retina cells released accumulated [ 3 H ]GABA ( γ-aminobutyric acid) when stimulated by l-glutamate, N-methyl- d-aspartate (NMDA) and kainate. In the absence of Mg 2+, dopamine at 200 μM (IC 50 60 μM), inhibited in more than 50% the release of [ 3 H ]GABA induced by l-glutamate and NMDA, but not by kainate. This effect was not blocked by the D 1-like dopamine receptor antagonist, R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH 23390), neither by haloperidol nor spiroperidol (dopamine D 2-like receptor antagonists). The dopamine D 1-like receptor agonist R(+)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,diol hydrochloride (SKF 38393) at 50 μM, but not its enantiomer, also inhibited the release of [ 3 H ]GABA induced by NMDA, but not by kainate; an effect that was not prevented by the antagonists mentioned above. (±)-6-Chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (SKF 812497) had no effect. Neither 8BrcAMP (5 mM) nor forskolin (10 μM) inhibited the release of [ 3 H ]GABA. Our results suggest that dopamine and (+)-SKF 38393 inhibit the glutamate and NMDA-evoked [ 3 H ]GABA release through mechanisms that seem not to involve known dopaminergic receptor systems.