Interleukin-2 Modulates Evoked Release of [3H]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 [3H]dopamine ([3H]DA) and γ-[3H]-aminobutyric acid ([3H]GABA). At low concentrations (10−13-10−12M), IL-2 potentiated [3H]DA release evoked by the excitatory amino acids N-methyl-D-aspartate (NMDA) and kainate, whereas higher IL-2 concentrations (10−9-10−8M) had no effect. IL-2 (10−14-10−8M) modulated K+-evoked [3H]DA release in a biphasic manner, with low concentrations (10−12-10−11M) of IL-2 potentiating and higher concentrations (10−9-10−8M) inhibiting K+-induced [3H]DA release. IL-2 (10−14-10−8M) by itself failed to alter spontaneous [3H]DA release. The inhibition by IL-2 of K+-evoked [3H]DA release was reversible and not due to neurotoxicity, as preexposure to IL-2 (10−8M) had no significant effect on the subsequent ability of dopaminergic cells to take up and to release [3H]DA. Under our experimental conditions, IL-2 (10−8 M) did not alter Ca2+-independent [3H]GABA release evoked by either K+ or NMDA. The results of this study indicate that IL-2 is able to potentiate [3H]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.