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 gamma-[3H]-aminobutyric acid ([3H]GABA). At low concentrations (10(-13)-10(-12) M), 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(-8) M) had no effect. IL-2 (10(-14)-10(-8) M) modulated K(+)-evoked [3H]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 [3H]DA release. IL-2 (10(-14)-10(-8) M) 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(-8) M) 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 Ca(2+)-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.
Douglas Hospital Research Center, Quebec, Canada.
R
R
Alonso
I
I
Chaudieu
J
J
Diorio
A
A
Krishnamurthy
R
R
Quirion
P
P
Boksa
D000818:Animals; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism*; D007376:Interleukin-2 / Q000494:pharmacology*; D007608:Kainic Acid / Q000494:pharmacology; D008636:Mesencephalon / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D016202:N-Methylaspartate / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D014316:Tritium; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D007376:Interleukin-2; D014316:Tritium; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D011188:Potassium; D007608:Kainic Acid; D004298:Dopamine