INTERLEUKIN-2 MODULATES EVOKED RELEASE OF [H-3] DOPAMINE IN RAT CULTURED MESENCEPHALIC CELLS

Mesencephalic cell cultures were used as a model to investigate the ef fects of interleukin-2 (IL-2) on evoked release of [H-3]dopamine ([H-3 ]DA) and gamma-[H-3]-aminobutyric acid ([H-3]GABA). At low concentrati ons (10(-13)-10(-12) M), IL-2 potentiated [H-3]DA release evoked by th e excitatory amino acids N-methyl-D-aspartate (NMDA) and kainate, wher eas higher IL-2 concentrations (10(-9)-10(-8) M) had no effect. IL-2 ( 10(-14)-10(-8) M) modulated K+-evoked [H-3]DA release in a biphasic ma nner, with low concentrations (10(-12)-10(-11) M) of IL-2 potentiating and higher concentrations (10(-9)-10(8) M) inhibiting K+-induced [H-3 ]DA release. IL-2 (10(-14)-10(-8) M) by itself failed to alter spontan eous [H-3]DA release. The inhibition by IL-2, of K+-evoked [H-3]DA rel ease was reversible and not due to neurotoxicity, as preexposure to IL -2 (10(-8) M) had no significant effect on the subsequent ability of d opaminergic cells to take up and to release [H-3]DA. Under our experim ental conditions, IL-2 (10(-8) M) did not alter Ca2+-independent [H-3] GABA release evoked by either K+ or NMDA. The results of this study in dicate that IL-2 is able to potentiate [H-3]DA release evoked by a num ber of different stimuli, including K+ depolarization and activation o f both NMDA and non-NMDA receptor subtypes in mesencephalic cell cultu res. IL-2 is active at very low concentrations, a finding that indicat es a potent effect of IL-2 on dopaminergic neurons and implicates a ph ysiological role for this cytokine in the modulation of DA release.