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 effects 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 concentrations (10(-13)-10(-12) M), IL-2 potentiated [H-3]DA release evoked by the excitatory amino acids N-methyl-D-aspartate (NMDA) and kainate, whereas 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 manner, 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 spontaneous [H-3]DA release. The inhibition by IL-2, of K+-evoked [H-3]DA release was reversible and not due to neurotoxicity, as preexposure to IL-2 (10(-8) M) had no significant effect on the subsequent ability of dopaminergic cells to take up and to release [H-3]DA. Under our experimental 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 indicate that IL-2 is able to potentiate [H-3]DA release evoked by a number of different stimuli, including K+ depolarization and activation of both NMDA and non-NMDA receptor subtypes in mesencephalic cell cultures. IL-2 is active at very low concentrations, a finding that indicates a potent effect of IL-2 on dopaminergic neurons and implicates a physiological role for this cytokine in the modulation of DA release.