Interleukin‐2 Modulates Evoked Release of [³H]Dopamine in Rat Cultured Mesencephalic Cells

Abstract

Abstract: Mesencephalic cell cultures were used as a model to investigate the effects of interleukin‐2 (IL‐2) on evoked release of [ 3 H]dopamine ([ 3 H]DA) and γ‐[ 3 H]‐aminobutyric acid ([ 3 H]GABA). At low concentrations (10 −13 ‐10 −12 M ), IL‐2 potentiated [ 3 H]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 [ 3 H]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 [ 3 H]DA release. IL‐2 (10 −14 ‐10 −8 M ) by itself failed to alter spontaneous [ 3 H]DA release. The inhibition by IL‐2 of K + ‐evoked [ 3 H]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 [ 3 H]DA. Under our experimental conditions, IL‐2 (10 −8 M) did not alter Ca 2+ ‐independent [ 3 H]GABA release evoked by either K + or NMDA. The results of this study indicate that IL‐2 is able to potentiate [ 3 H]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.